U.S. patent number 8,438,042 [Application Number 10/134,424] was granted by the patent office on 2013-05-07 for instruments and methods for obtaining informed consent to genetic tests.
This patent grant is currently assigned to National Biomedical Research Foundation. The grantee listed for this patent is Fred David Ledley. Invention is credited to Fred David Ledley.
United States Patent |
8,438,042 |
Ledley |
May 7, 2013 |
**Please see images for:
( Certificate of Correction ) ** |
Instruments and methods for obtaining informed consent to genetic
tests
Abstract
This invention provides an instrument for obtaining consent for
a genetic test that comprises three or more integrated elements
including an information element for conveying information to an
individual concerning a genetic test, and instruction element for
use by a practitioner in instructing individuals on the genetic
test and use of the instrument, a collection element for collecting
an individual's medical and family history, a assessment element
for assessing the individual's retention and understanding of
information concerning a genetic test, a certification element for
certifying the individual's consent to said tests, as well as
housekeeping elements useful for recording a medical record,
labeling a sample, and billing. Also provided is a method for
obtaining informed consent for a genetic test using an integrated
instrument. The instruments and methods disclosed have utility in
obtaining informed consent for genetic tests.
Inventors: |
Ledley; Fred David (Needham,
MA) |
Applicant: |
Name |
City |
State |
Country |
Type |
Ledley; Fred David |
Needham |
MA |
US |
|
|
Assignee: |
National Biomedical Research
Foundation (Bethesda, MD)
|
Family
ID: |
29249230 |
Appl.
No.: |
10/134,424 |
Filed: |
April 25, 2002 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20030204418 A1 |
Oct 30, 2003 |
|
Current U.S.
Class: |
705/3; 702/84;
434/322; 379/265.01; 600/300; 702/179; 702/20 |
Current CPC
Class: |
G16H
10/60 (20180101); G16H 10/40 (20180101); G06Q
10/10 (20130101); G16B 50/20 (20190201); G16B
50/40 (20190201); G16H 40/20 (20180101); G16H
50/30 (20180101); G16B 50/00 (20190201) |
Current International
Class: |
G06Q
50/00 (20120101) |
Field of
Search: |
;705/2-3 ;600/300
;379/265,265.01 ;364/400 ;434/322 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Advisory Committee on Genetic Testing Code of Practice and Guidance
on Human Genetic Testing Services Supplied Direct to the Public by
John Polkinghome KBE FRS, Aug. 1997). cited by examiner .
Advisory Committee on Genetic Testing Code of Practice and Guidance
on Human Genetic Testing Services Supplied Directly to the Public
by John Polkingham (Sep. 1997). cited by examiner .
"Attachment to AHA Regulatory Advisory: Model HOPPA notice of
privacy practices," Feb. 13, 2001. cited by applicant .
"GeneScreen: bonemarrowtest.com"
www.genescreen.com/bone.sub.--marrow.sub.--testing.asp, printed
Dec. 11, 2001, 4 pages. cited by applicant .
Perr I. N., "Privilege, confidentiality and patient privacy: status
1980," J. Forensic Sci. 26:109-115 (1981). cited by applicant .
Williams-Jones, "Re-framing the discussion: Commercial genetic
testing in Canada,"Health Law Journal (Canada) 7:49-67 (1999).
cited by applicant .
Yan et al., "Genetic testing--present and future," Science
289(5486):1890-1892 (2000). cited by applicant .
McKinnon et al, The Familial cancer program of the Vermont Cancer
Center: Development of a cancer genetics program in a rural area.
Journal of Genetic Counseling, 6(2): 131-145, 1997. cited by
applicant .
Tarczy-Hornoch et al., "Creation and Maintenance of Helix, a Web
Based Database of Medical genetics Laboratories, to Serve the Needs
of the Genetics Community", Proc AMIA Symp (1998) pp. 1-5. cited by
applicant .
Non-Final Office Action dated Apr. 5, 2012 in related U.S. Appl.
No. 13/205,556. cited by applicant .
Attachment to AHA Regulatory Advisory: Model HOPPA notice of
privacy practices. Feb. 13, 2001. cited by applicant .
Examiner's Answer dated Jul. 20, 2009 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated Apr. 1, 2005 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Apr. 17, 2009 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Aug. 1, 2005 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Aug. 19, 2005 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated Aug. 26, 2003 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Dec. 10, 2007 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated Feb. 10, 2006 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated Feb. 26, 2007 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated Dec. 4, 2001 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Feb. 5, 2010 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Feb. 8, 2006 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Feb. 7, 2008 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Jul. 13, 2006 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Jul. 6, 2006 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated Jun. 14, 2007 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Mar. 4, 2005 from related U.S. Appl. No.
10/200,978. cited by applicant .
Office Action dated May 20, 2004 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Nov. 17, 2006 from related U.S. Appl. No.
09/630,631. cited by applicant .
Office Action dated Sep. 17, 2008 from related U.S. Appl. No.
10/200,978. cited by applicant .
Perr I.N., Privilege, confidentiality and patient privacy: status
1980, J. Forensic Sci, 26:109-115 (1981). cited by applicant .
Tarczy-Hornoch, et al, Creation and maintenance of helix, a web
based database of medical genetics labaoratories, to serve the
needs of the genetics community, (1998), Proc AMIA Symp, pp. 1-5.
cited by applicant .
Williams-Jones, Re-framing the discussion: Commercial genetic
testing in Canada, Health Law Journal (Canada) 7:49-67 (1999).
cited by applicant .
Yan et al., Genetic testing--present and future, Science
289(5486):1890-1892 (2000). cited by applicant .
U.S. Office Action for U.S. Appl. No. 09/630,631, dated Apr. 17,
2009. cited by applicant .
Decision of the Patent Trial and Appeal Board in related U.S. Appl.
No. 09/630,631 (Appeal No. 2011-006312) issued Nov. 19, 2012. cited
by applicant.
|
Primary Examiner: Frenel; Vanel
Attorney, Agent or Firm: Foley & Lardner LLP
Claims
I claim:
1. A kit, comprising: an instrument embodied on a computer
recordable medium for obtaining from an individual informed consent
prior to conducting a genetic test on said individual, said
instrument comprising: (a) an information element, wherein said
information element comprises information required for obtaining
the individuals about the genetic test; (b) an instruction element,
integrated with said information element, wherein said instruction
element comprises directions on how to instruct the individual in
the information in the information element; (c) a certification
element, integrated with said instruction and said information
elements; and (d) an assessment element, integrated with said
information and said instruction elements, wherein said assessment
element comprises text questions covering information presented in
the information element and instruction element; wherein said
information element, instruction element, certification element and
assessment element is each through a virtual provider.
2. A kit according to claim 1 wherein said genetic test is selected
from the group consisting of a test for one gene, a test for more
than one gene, a test for related genes, a test for genes
associated with a specified clinical outcome and a gene screen
test.
3. A kit according to claim 1 comprising at least one additional
element selected from the group consisting of a collection element,
a labeling element, a billing element, a recording element, a
training element, a quality control element, and an indemnification
element, wherein said additional element interacts with said
individual through a virtual provider.
4. A kit according to claim 3 wherein said additional element
comprises a collection element.
5. A kit according to claim 4, additionally comprising at least one
element selected from the group consisting of a labeling element, a
billing element, a recording element, a training element, a quality
control element and an indemnification element.
6. The kit according to claim 1 wherein said instruction element
comprises a checklist.
7. The kit according to claim 1 wherein said assessment element
comprises questions about one or more of the following selected
from the group consisting of the genetic test, the risks and
benefits of the genetic test, clinical practice guidelines,
recommendations, and possible clinical actions in response to the
genetic test results.
8. The kit according to claim 7 wherein the assessment element
further comprises answers to each of the questions and procedures
for responding to incorrect questions answers.
9. The kit according to claim 1 wherein the questions covering
information presented in the information element and instruction
element concern a genetic test for one gene, more than one gene,
related genes, a clinical outcome or a gene screen to be performed,
possible test results, DNA banking, the medical significance of
potential test results, standard of care recommendations concerning
such tests, the choices available based on the test results, the
specific benefits and risks of performing the tests, the procedure
for obtaining a sample and performing a test, the disposition and
potential future use of the sample as well as the test results,
guidelines for protecting the privacy and confidentiality of the
individual, and legal issues regarding liability.
10. A method for obtaining through a virtual provider informed
consent from an individual prior to conducting a genetic test on
said individual, comprising the steps of: (a) conveying to the
individual information concerning said genetic test using an
information element of an integrated instrument embodied on a
computer recordable medium for obtaining informed consent to the
genetic test, said instrument including an information element, an
instruction element integrated with said information element, a
certification element integrated with said information and said
instruction elements; and an assessment element, integrated with
said information and said instruction elements, (i) wherein said
information element comprises information required for obtaining
the individual's consent for the genetic test, (ii) wherein said
instruction element directs the virtual provider on how to instruct
the individual as to the information in the information element,
and (iii) wherein said assessment element comprises text questions
covering information in said information element and said
instruction element to assess the individual's understanding of the
test to be performed; (b) instructing the individual according to
the directions contained in said instruction element; (c)
certifying the individual's consent for said test using said
certification element; (d) assessing the individual's retention and
comprehension of the information concerning the genetic test using
said assessment element; and optionally (e) obtaining a sample from
the individual and performing said genetic test on said sample to
obtain a result; wherein at least steps (a)-(d) are facilitated
through a virtual provider.
11. The method according to claim 10, wherein said integrated
instrument additionally includes a virtual provider collection
element integrated with said information and said instruction
elements, and said method comprises the additional step of
collecting a personal medical history and family history using said
collection element.
12. The method according to claim 10 wherein said integrated
instrument additionally includes a virtual provider labeling
element integrated with said information and said instruction
elements, and said method includes the additional step of labeling
a sample with the identity of the individual using said labeling
element.
13. The method according to claim 10 wherein said integrated
instrument additionally includes a virtual provider recording
element integrated with said information and said instruction
elements, and said method includes the additional step of recording
information concerning the informed consent process using said
recording element.
14. The method according to claim 10 wherein said genetic test is
selected from the group consisting of a test for one gene, a test
for more than one gene, a test for related genes, a test for genes
associated with a specified clinical outcome and a gene screen
test.
15. The method according to claim 10 wherein said assessment
element comprises questions about one or more of the following
pieces of information selected from the group consisting of the
genetic test, the risks and benefits of the genetic test, clinical
practice guidelines, recommendations, and possible clinical actions
in response to the genetic test results.
16. The method according to claim 15 wherein the questions in the
assessment element concern content from the information element and
the instruction element, and wherein the assessment element further
comprises answers to each of the questions and procedures for
responding to incorrect answers.
17. The method according to claim 10 wherein the assessment element
includes text comprising questions covering information presented
in the information element and instruction element concerning a
genetic test for one gene, more than one gene, related genes, a
clinical outcome or a gene screen to be performed, possible test
results, DNA banking, the medical significance of potential test
results, standard of care recommendations concerning such tests,
the choices available based on the test results, the specific
benefits and risks of performing the tests, the procedure for
obtaining a sample and performing a test, the disposition and
potential future use of the sample as well as the test results,
guidelines for protecting the privacy and confidentiality of the
individual, and legal issues regarding liability.
Description
FIELD OF THE INVENTION
This invention provides novel instruments and methods for obtaining
informed consent for genetic tests.
BACKGROUND OF THE INVENTION
The human genome project has been undertaken with the expectation
that the sequences of genes that comprise the genome are
determinants of individual development, health, and disease.
Variation in gene sequences, variations in the level, location, or
timing of expression of a gene, and variation in the physical,
chemical, or dynamic characteristics of the products expressed from
a gene are known to underlie many aspects of human individuality
including physical and mental characteristics, growth, longevity,
health, and disease. An objective of genomic research is the
discovery, development and implementation of genetic tests that can
be used to determine how the genes of an individual predispose that
individual to various clinical outcomes. Genetic tests are expected
to have a central role in routine health, wellness, and disease
management, enabling predisposition testing and interventions to
prevent disease, providing early diagnosis, and optimizing
pharmacological interventions with drugs that are likely to be safe
and effective for an individual.
The utilization of genetic tests and the interpretation of genetic
tests results are more complex than conventional diagnostic
testing. The number of genetic tests that will be available from
human genomic research is very large compared to the number of
conventional diagnostic tests. The genome project is expected to
reveal 30,000-100,000 genes and >10,000,000 discrete genetic
variations that may be developed into genetic tests with utility in
predicting specific health outcomes. Few individuals or healthcare
practitioners are familiar with the many genes different already
known to be associated with specific health outcomes. Few have the
ability to remain current with the rapidly emerging literature in
this field. The effective and ethical use of genetic tests requires
that individuals have sufficient information about the tests to
decide whether to have the test done and to make efficacious use of
the test result. This requires that individuals have access to
information concerning the potential benefits of genetic testing,
the procedures involved in genetic testing, and the potential risks
to health and privacy. Because of the unique nature of genetic
testing, good medical practice and statutory requirements in some
states require that an informed consent be obtained from an
individual before a sample is obtained and a genetic test is
performed. To provide a valid informed consent, an individual must
have been given and must retain and understand sufficient
information concerning the test, the DNA sample, the potential use
of genetic information that may be obtained from the sample, and
the potential benefits and risks associated with the test to make
an informed decision regarding the test.
Genetic testing is typically initiated by health care practitioners
(including primary or subspecialty physicians or practitioners
specialized in genetics, such as MD, PhD, or MA/MS trained
geneticists or genetic counselors), and informed consent is
obtained by the practitioner during a meeting with the individual.
During this meeting, the practitioner must provide the individual
with information sufficient for the individual to make an informed
choice and to certify their consent to the testing procedure. After
certification, samples are typically obtained by the health care
practitioner or a designated blood drawing facility and tests are
then performed by certified laboratories. The test result is
reported from the laboratory to the practitioner and/or to the
individual. Many practitioners do not have sufficient training in
genetics, knowledge relating to individual genetic tests, or time
to adequately provide individuals with the information required to
provide a legally binding informed consent.
The process of obtaining informed consent is described in many
textbooks, articles, reports, and recommendations. In current
practice, information about genetic tests is collected by
practitioners and individuals from a variety of sources including
textbooks of medicine or genetics, as well as articles in medical
journals, courses for continuing medical education, government
agencies, disease advocacy groups, biotechnology companies,
academic research groups, the Internet, and articles in the lay
press. This information, as well as information about the process
of obtaining a genetic test, and the use of genetic test results is
discussed with the individual in an ad hoc manner. Many sources of
information are written at a level appropriate for healthcare
practitioners. Few are appropriate for individuals in the general
public. Moreover, information gleaned from multiple sources is
often conflicting and incomplete. Few sources of information are
validated in clinical studies to demonstrate that the content and
mode of presentation results in comprehension and retention by the
individual.
Documents by which an individual can certify their consent to a
genetic test are known in the art. Such documents focus primarily
on legal issues related to genetic testing such as the technical
and predictive limitations of genetic testing, potential errors in
diagnosis and interpretation, the disposition of the DNA sample,
and the reporting of test results. Informed consent documents are
typically generic, i.e., they address issues that are relevant to
many different genetic tests and clinical outcomes rather than
being specific to particular genetic test, genetic tests for
related genes, or a specific clinical outcome.
Because of the complexity of genetic information, the widespread
lack of professional training in genetics and procedures for
delivering genetic services, and the lack of validated resources
for providing genetic services, surveys suggest that <10% of
practitioners feel that they are capable of adequately providing
such services. Moreover, despite laws in some states that require
informed consent be obtained before genetic tests are performed,
data demonstrates that many genetic tests are performed without any
informed consent being obtained or with inadequate informed
consent.
SUMMARY OF THE INVENTION
The inventor has determined that an instrument for obtaining
informed consent comprising integrated elements with information
for the individual, instruction for the practitioner, and materials
for certifying an individual's consent and, optionally, elements
for processing the genetic record, sample collection, and billing
has utility in assisting practitioners to obtain meaningful and
legally binding informed consent. This instrument may be validated
to establish that it is effective in establishing understanding,
comprehension, and effective use of the test and test result. The
instrument described in this invention provides an individual with
information about a genetic test for one gene, more than one gene,
related genes, genes associated with a clinical outcome or for a
gene screen and assists the provider in obtaining a valid informed
consent and performing other procedures associated with genetic
testing.
The instrument comprises an information element, an instruction
element and a certification element. The elements are integrated.
The information element contains information sufficient for an
individual to provide a valid informed consent. This element is
integrated with an instructional element for the practitioner that
contains more detailed reference information on the gene, gene
test, or clinical outcome that is the subject of the test as well
as stepwise directions on how to instruct the individual in the
information in the information element and materials designed to
support such instruction. The integrated instrument contains both
informational materials required by the practitioner and the
individual as well as worksheets, checklists, forms, illustrative
materials and other materials required to carry out these steps in
an integrated manner. The information element contains basic
information for individuals about the genetic test including text
and illustrative materials in the primary language of the
individual and at a level of comprehension appropriate for the
general population. It is generally considered that materials
intended for comprehension by the general population should not
exceed an 8-10.sup.th grade level. The information element is
designed to provide individuals with information that is accurate,
timely, and useful and considered by experts to be sufficient for
an individual to make an informed decision to proceed with a
genetic test. The information element may contain illustrative
materials as well as supplemental information about genetics,
genetic tests, or a clinical outcome, or references or links to
more advanced information available in printed materials or
electronic medium.
The instruction element directs the practitioner how to present
information to individuals and how to obtain informed consent using
the instrument. This element includes stepwise instructions on the
use of the instrument and each of the elements comprising the
instrument, reference information at the level of the practitioner
on medical genetics, the genetic test, and related clinical
outcomes, and answers to questions that are frequently asked by
individuals during the consent process. The instruction element
preferably contains a checklist to document that the practitioner
has followed each of the steps required for use of the instrument.
The instruction element may contain illustrative materials for use
by the practitioner in presenting information to the individual,
for example, props, diagrams, worksheets, objects, exercises,
questions, or games that can be used to improve the individuals
retention and comprehension of the information. The instruction
element may also include a worksheet to assist the practitioner in
calculating an individual's genetic risk of a clinical outcome
based on genetic test results as well as information from the
individual's medical history or family history.
The instruction element advantageously reduces the impact of the
practitioner's subjectivity. It is well known that, for example,
validated instruments for neuro-psychological testing require the
practitioner to adhere strictly to the instruction set in order
achieve valid testing results. In this invention, the instruction
element provides the means for standardization of the procedures
employed by the practitioner in obtaining informed consent, and
enables consent to be obtained in a validated manner. In addition,
it is generally recognized that information presented to
individuals and the practices of the practitioner should be
non-directive. The standardized and validated information element
and instruction elements minimize unintentional bias and improve
the quality and ethics of the consent and the consent process.
The instrument of this invention also includes a certification
element. The certification element comprises a legal document in
which the individual consents to the genetic test before any
required witnesses, who certify that the individual has consented
to the genetic test.
Optionally included in the instruments of the invention are various
other elements, to wit, an assessment element, a collection
element, a labeling element, a billing element, a recording
element, a training element, a quality control element and an
indemnification element. One or any more than one of these elements
may be included with the information, the instruction and the
certification elements that comprise the instrument of the
invention. Preferred elements to be included comprise the
assessment element or the collection element, or both. Any optional
element included in the instrument is integrated with one or more
of the three essential elements.
The assessment element assesses the individual's retention and
understanding of information contained in the information element
and instruction element. The assessment element comprises questions
about the genetic test, the risks and benefits of the test,
clinical practice guidelines, recommendations, and possible
clinical actions in response to the test results. The assessment
element is integrated with the information element, in that the
questions in the assessment element concern content from the
information element, as well as the instruction element, which
provides correct answers to each of the questions and procedures
for responding to incorrect questions. The assessment element is
intended to determine whether the individual satisfies the minimum
standards of retention and understanding sufficient to provide a
valid informed consent. The assessment also serves as an internal
form of quality control on the ability of the practitioner to
practice this method.
The integrated collection element assists the provider in obtaining
information from an individual concerning their personal medical
history and family history that is useful in deciding whether or
not to have a genetic test performed and quantitatively determine
the individual's genetic risk. This element is integrated with the
information element which describes, for example, how an
individual's family history impact their risk of a clinical
outcome, as well as the instruction element which provides the
practitioner with the ability to collect the personal medical
history and family history and analyze this information to make a
preliminary assessment of risk.
The other optional elements provide "housekeeping" functions. The
labeling element and the billing element further assists the
practitioner in processing the sample for genetic testing,
establishing a genetic record, and obtaining payment for the test.
The recording element ensures that a record of the informed consent
process and the certification is established. The training element
trains practitioners in the use of the instrument, the quality
control element assesses the performance of the user against
performance standards, and the indemnification element provides an
indemnification form for practitioners who use the instrument to
obtain consent against claims that adequate informed consent was
not properly obtained.
The method described in this invention involves the use of an
integrated instrument to obtain valid informed consent. This method
comprises, briefly, the steps of transmitting to the individual
information on the genetic test and on the process of testing,
instructing the individual with respect to the genetic test and the
testing process and obtaining the individual's certified consent to
the test using an integrated instrument. The method may optionally
include the steps of collecting a personal medical history and
family history using an integrated collection element, assessing
the individual's retention or comprehension of this information
using an integrated assessment element, labeling the sample with
information required for proper sample handling using an integrated
labeling element, and recording information concerning the informed
consent process, the test to be performed, and the individual's
medical and family history in a medical record using an integrated
recording element. The method preferably includes the two steps of
collecting and/or assessing. It may include any one or more of the
remaining steps of labeling, billing training, providing quality
control, indemnification and recording using integrated elements.
Preferably these steps are performed using integrated elements.
One or more of the elements of the instrument may be posted to make
it generally available to individuals or practitioners, by placing
it on a web site, and providing it as a resource in printed or
electronic medium accessible to individuals or practitioners, or
incorporating it in policies, practices, guidelines,
recommendations, training materials, or lessons and using
integrated elements for one or more of the steps of informing,
instructing, assessing, collecting, certifying, labeling, and
recording. Preferably the information element and/or the
instruction element is posted.
DETAILED DESCRIPTION OF THE INVENTION
A. Definitions and General Information
"Genetic test", "gene test", "test", or "genetic testing" mean the
analysis of DNA, RNA, protein, or other biological materials in a
sample from an individual to determine, without limitation, the
sequence or structure of one, or more than one, gene, the presence
or absence of one, or more than one, genetic marker, variance,
variation, mutation, polymorphism, or micro satellite sequence
associated with a gene, the presence of one, or more than one,
viral sequence, viral-like sequence, or repetitive sequence, a
haplotype or genotype spanning one, or more than one, gene, the
number of copies of one, or more than one, gene, the amount or
characteristics of RNA or protein expressed from one, or more than
one, gene, the biological function of one, or more than one, gene,
the arrangement of genes within the genome, the chromosome number,
or integrity, modification, or structure of DNA and chromosomes.
Many gene tests are useful in medicine for determining and
individual's risk of a clinical outcome including diagnosing
genetic disease, determining an individual's propensity to
multifactorial diseases, and/or predicting an individual's response
to therapeutic drugs. Genetic tests have been developed for many
inherited diseases including, for example, Huntington's Disease,
Cystic Fibrosis, and Phenylketonuria. Genetic tests have also been
developed for genes that predispose to common, multifactorial
diseases including, for example, atherosclerosis, heart failure,
stroke, anemia, cancer, clotting disorders, dementia, endocrine
diseases, osteoporosis, and pulmonary diseases. Genetic tests have
also been described which predict the pharmacokinetic and
pharmacodynamic characteristics of many drugs including, for
example, drugs for the treatment of elevated cholesterol, drugs to
treat cancer, drugs to reduce hypertension, and drugs to treat
dementia. The term genetic test includes any test which determines
the structure, characteristics, amount, or activity of certain
chemical entities that reflect the structure or function of one
gene or more than one gene.
A common form of a genetic test involves the sequencing of one or
more genes to determine whether the sequence corresponds to a
sequence known to encode a gene product associated with normal
biological or clinical activity or having a variant sequence that
encodes a gene product that correlates with an abnormal function,
disease, or clinical outcome. Gene sequences can be determined from
gels, using automated sequencing, gene chips, hybridization to
selected or random nucleotide sequences, mass spectroscopy or other
methods well known in the art. Methods for selectively determining
the sequence of one, or more than one, specific bases within a gene
or the sequence of a region of a gene known to be a marker for
specific health outcomes or to be associated with specific clinical
outcomes are also well known in the art. A genetic test may
identify a single variance within a gene or multiple variances
within a gene. A genetic test may also identify one or more
variances in more than one gene.
One form of a genetic test is a "gene screen" which identifies a
large number of variances within one gene or many different genes,
potentially every gene in the genome. A gene screen may identify
variances in genes that are related through a common pathway,
process, or clinical outcome and/or genes that are not related.
Such tests raise particularly difficult issues for obtaining
informed consent. A specific embodiment of this invention is an
instrument for obtaining informed consent for a gene screen.
Another common form of genetic test well known in the art
quantifies the amount or structure of mRNA for one gene or many
different genes in a sample. Other forms of genetic tests involve
identification and analysis of specific proteins, or structurally
variant forms of proteins by mass spectroscopy, electrophoresis, or
by binding to natural or synthetic substrates or antibodies using
methods well known in the art.
"Sample" means an aliquot of material from an individual, for
example, blood, tissue, hair, skin cells, mucosal cells, or cells
from other parts of the body, secretions such as saliva, mucous,
urine, feces or other bodily tissues, or fluids, useful for genetic
testing. Sample also means DNA, RNA, protein or other chemical
entities useful for genetic testing that are extracted or purified
from such materials. The term refers to, without limitation, any
substance or chemical entity derived directly or indirectly from an
individual that contains DNA, RNA, protein, or other materials
suitable for performing a genetic test. A sample may contain
sufficient material to perform one genetic test or a series of
genetic tests over time. The term "label" is generally known in the
art and refers to information that is attached to or otherwise
associated with a sample or sample collection device which may
contain information concerning the handling and disposition of the
sample, the test to be performed, and identifying information
concerning the individual.
"Sample collection device" is generally known in the art and
includes any device for obtaining samples for genetic tests and
placing them in a format that can be delivered to the site where
the sample can be extracted and the test can be performed. Examples
of sample collection devices for genetic testing are known in the
art. Sample collection devices may incorporate, for example, filter
paper or tubes which hold the sample for transport to a laboratory,
extraction of DNA or other components of the sample, storage of the
sample, DNA banking, or performing one or more steps of the genetic
test. It will be recognized that several difference devices may be
used in the course of obtaining and processing a sample and
performing a genetic test and storing the sample, and that multiple
labels may be required to transmit information through the course
of the sample handling and testing procedures. Samples can be
collected using routine procedures for blood drawing and commonly
employ tubes designed to enable the separation of nucleated cells,
plasma or serum. Specialized devices are also known in the art
including several devices that are approved by the FDA for sample
collection. An exemplary device is the OraSure Oral Specimen
Collection Device from Orasure Technologies, Inc. which is an
FDA-approved device that can be used for the collection of DNA from
the oral mucosa for clinical applications. Another exemplary device
is S&S 903 Specimen Collection Paper from Schleicher &
Schuell, GmbH which is also a FDA listed device widely used for
sample collection, including genetic studies. S&S 903 Specimen
Collection Paper, is used widely for newborn screening and has also
been used for genetic studies. S&S 903 Specimen Collection
Paper has also been incorporated into single and multi-part forms
and forms and customized printing is available from the
manufacturer with biologically inactive inks and glues that enable
the paper to incorporate information or codes for patient
identification, processing, and lot traceability. The 903 device
can be used to collect blood or body fluids such as urine, tears,
or saliva which are spotted and dried onto the 903 paper. In this
form the sample is stable and can be mailed to centralized labs for
analysis, sample extraction, or DNA banking.
A gene test may be performed using a "diagnostic product" that
provides one or more than one of the reagents and materials
required to form said test and may include a sample collection
device. A diagnostic product typically comprises a kit containing
reagents and materials that have been subjected to quality control
and premeasured so that the test can be performed effectively by a
technician, automated laboratory, or even an individual. Diagnostic
products may be reviewed and approved by the Food and Drug
Administration as In Vitro Diagnostics. Most genetic testing today
is not performed using approved diagnostics, but rather performed
under FDA "home brew" guidelines using analyte specific reagents.
The term diagnostic product as used herein includes analyte
specific reagents, sample collection devices, or other reagents or
materials used to perform genetic tests.
"Banking" or "DNA banking" means the storage of a sample intended
for future genetic testing. Since the gene sequences of aggregate
somatic cells do not change over time (unless the cells are clonal
and/or malignant), a sample obtained for one genetic test can be
banked and additional tests can be performed at a later time.
Informed consent is commonly required for DNA banking. Such consent
must describe the potential uses of the sample and the final
disposition of the sample. Potential uses may include retesting for
quality control, genomic research, or additional tests for the
benefit of the individual that may be requested by the individual
or practitioner. Such consent should also state whether a sample
will be stored indefinitely or destroyed. Preferably the informed
consent for a genetic test includes informed consent for banking,
the permitted uses of the banked sample in the future, and the
disposition of the banked sample.
"Chemical entity" means proteins, protein derivatives (such as
glycoproteins, lipoproteins, or phosphoproteins), lipids,
carbohydrates, small-molecule organic compounds, and inorganic
compounds measured in tissue or body fluids whose structure,
activity, characteristics, amount, location, or activity reflects
the structure or function of one or more genes. It is recognized
that tests on chemical entities often enable direct inferences to
be made concerning the structure or activity of one or more genes.
For example, electrophoresis of hemoglobin extracted from red blood
cells can reveal a change in the hemoglobin molecule caused by the
sickle cell mutation in the hemoglobin gene; an increase in the
amount of phenylalanine in the blood or urine can reveal the
presence of mutations in the gene for phenylalanine hydroxylase;
the concentration of salts in sweat can reveal the presence of
mutations in the CFTR gene, the ability of a specific monoclonal
antibody to hybridize to a tumor cell may determine whether a
genetic rearrangement has taken place; and a measure of Thiopurine
Methyltransferase enzyme activity may reveal the presence of
mutations in the TPMT gene. One skilled in the art will recognize
that it is frequently more convenient and cost effective to
determine the structure or activity of a protein or to measure
metabolites in blood or urine than to perform an analysis directly
on DNA or RNA. Such tests can be used interchangeably with tests
that directly analyze DNA or DNA in the present invention. Many
tests can reveal evidence indicating variations in gene sequences,
expression or function including, for example, tests for proteins
in serum, blood cells, tissues, assays for the expression of
specific genes measured at the RNA or protein level, and assays for
metabolites that are characteristic of specific gene functions or
dysfunctions. It will be recognized that tests for chemical
entities other than DNA or RNA may not be explicitly included in
guidelines or statutes mandating informed consent. Nevertheless,
the information that can be gained from such tests is often
equivalent to that obtained through the analysis of DNA and RNA and
presents similar benefits and risks to the individual. This
invention specifically relates to tests performed on any chemical
entity as a genetic test.
A "gene" is a linear sequence of nucleotides that encode or control
a biological function. Genes typically direct the expression of RNA
or protein which may be directly responsible for carrying out the
function encoded by the gene, or the RNA or protein may be subject
to modifications to carry out such functions. The gene may include,
without limitation, introns, exons, promoters, or other sequences
as well as chemical modifications of the nucleic acids which are
involved in determining a biological function associated with that
gene including the activity, amount, structure, or location of a
chemical entity. Those skilled in the art will also recognize that
the term gene is also used to refer to a specific series of
nucleotides including characteristic variations that are associated
with a clinical outcome. For example, a CFTR gene with variations
that cause cystic fibrosis is often referred to as a "cystic
fibrosis gene", a BRCA1 gene with variations that cause breast
cancer is often referred to as a "breast cancer gene", and a
phenylalanine hydroxylase gene with mutations that cause
phenylketonirua is referred to as a "PKU gene."
It is recognized by the skilled artisan that the sequence of
nucleotides in the gene which encode its function may vary in
different individuals, and that variances or mutations within the
sequences of nucleotides of the gene may change its function. The
terms "mutation", "variation", "polymorphism", or "variance" refer
to sequences within a gene which may differ among individuals. The
term mutation is typically used to describe those variations that
alter a characteristic activity of a gene or a gene product such as
changes in the structure, activity, expression, availability,
modification, processing, specificity, or function. Mutation more
specifically describes those variations that impair activity of a
gene or a gene product or are associated with an adverse clinical
outcome. The terms "genetic marker", "polymorphism", or "single
nucleotide polymorphism (SNP)", are typically used to refer to
specific sequences within a gene that can differ among individuals
that are useful as markers to identify specific genes. Use of these
terms implies that the specific variation in sequence does not
alter the function of the gene, however, such sequences could be
associated with characteristic activity of the gene or gene product
or a specific clinical outcome. When a genetic variation is
associated with a specific clinical outcome, the variation, and the
gene that contains that variation, are said to "cause" or be
"linked" or "associated" with that clinical outcome. Those skilled
in the art recognize that a sequence variance which has detrimental
effects in one circumstance, can have no effect, or even have
beneficial effects in other circumstances, that sequence variances
that have biological effects can also be used as markers, and that
markers may be very closely linked with specific clinical outcomes
even if they are not causative. Specific embodiments of this
invention relate to sequence variations that are associated with a
specific clinical outcome either because the sequence variation
alters the biological function of a gene in a way that causes the
clinical outcome, or because the sequence variation is a marker
that is linked or associated with a clinical outcome. The skilled
artisan will recognize that it is often not known whether a
specific variance is a mutation or a polymorphism, that the terms
"variance", "variation", "mutation", "genetic marker",
"polymorphism", and "SNP" each refer to differences in gene
sequences, or positions in the genome where differences in the
sequence are found between different individual, and that these
terms are often used interchangeably in describing gene sequences
that may be the object of a genetic test.
Relationships among genes are recognized based on similarities in
structure and function, activities that contribute to common
biological pathways, or activities contributing to a common
pathological process or clinical outcome. "Gene family" means genes
that share common structural or functional characteristics or
activities. Some genes within a gene family may exhibit structural
similarities due to comparable function (analogy) or evolution
(homology) and may contain sequence identities, common motifs, or
common functional elements, and may often be located in contiguous
or closely linked regions of the chromosomes. It is recognized that
genes within a family often carry out analogous biological
functions, and that mutations in closely related genes can lead to
similar clinical outcomes. "Pathway" refers to a sequential or
intersecting set of biological functions. Several genes and gene
products are be typically involved in pathways for complex
biological function such as the synthesis of biological compounds,
the construction of cellular or somatic structures, or the
regulation of a process within the body. It is recognized that
genes that contribute to a common pathway often work in a
coordinated fashion, and that variances in any gene along the
pathway could alter the characteristic structure, level, or
expression of other genes as well as the end product. A disease,
disorder or clinical outcome can often involve multiple genes as
well as different variances in one or more than one gene. Genes are
said to be "related" if they comprise a gene family or are involved
in a common pathway, process, or clinical outcome.
The present invention relates to obtaining informed consent for
genetic tests for one or more than one variances in one gene or in
more than one gene. A preferred aspect of this invention of relates
to obtaining informed consent for genetic tests for more than one
gene where such genes are related members of a gene family, a
pathway, process, or clinical outcome. Obtaining informed consent
for such tests may require proportionally more information on the
part of the practitioner and understanding on the part of the
individual for the consent to be valid. In specific embodiments of
this invention, the genetic tests is for two genes where such genes
are related members of a gene family, a pathway, process or
clinical outcome, three such genes, five such genes, more than 5
such genes, more than 10 such genes, or more than 100 such genes.
In a specific embodiment of this invention the genetic test is a
gene that includes two or more than two genes that may not be
related, more than 10 genes, more than 100 genes, more than 1000
genes, or more than 10,000 genes.
"Disease" and "disorder" refer to recognized morbid or pathological
events and are commonly catalogued in textbooks of medicine and
standard classifications of disease such as the International
Classification of Disease (ICD). "Clinical outcome" means any
observable clinical event or observation including, for example,
disease, disorder, health, morbidity, or mortality; growth,
development, aging or longevity; the onset, progression, course,
remission, relapse, symptoms, signs, or pathology of a disease or
disorder; cognitive function, behavior, psychosis, or dementia; as
well as drug response, or drug toxicity or the response to any
intervention involving drugs, nutrition, lifestyle change,
education, or surgery as well as the application of non-allopathic
therapies such as, without limitation, traditional, herbal, or folk
medicines, nutricuticals, osteopathy, or chiropractic medicine. The
present invention relates preferably to genetic tests useful in the
field of medicine for predicting a clinical outcome or determining
the genetic risk of a clinical outcome.
The present invention is applicable to any clinical outcome known
in the art for which genetic tests may identify a risk factor for
that clinical outcome. A skilled artisan would recognize that the
present invention is not limited to diseases that are traditionally
identified as being genetic in origin but also to clinical outcomes
that are "multifactorial", i.e. associated with combinations of
genetic and environmental factors. This includes, for example,
clinical outcomes such as heart disease, hypertension, heart
failure, coronary vascular disease, cerebral vascular disease,
stroke, peripheral vascular disease, arthritis, rheumatoid
arthritis, Lupus Erythematosis (SLE), psoriasis, asthma, reactive
airway disease, COPD, osteoarthritis, osteoporosis, hearing loss,
cataracts, renal failure, nephritis, hepatic failure, hepatitis,
pancreatitis, diabetes, infection, cancer, drug toxicity, drug
resistance, drug dependence, neurological diseases, dementia,
Alzheimer's disease, psychosis, neuroses, and metabolic
diseases.
It is often important to perform genetic tests for multiple
variations that may occur in one gene, or more than one gene, to
determine an individual's risk of a multifactorial clinical
outcome. For example, a mutation in one gene may predispose an
individual to a high risk of a clinical outcome, which may be
increased or decreased by variations occurring in another related
gene. Many multifactorial diseases are also "polygenic", meaning
that they are associated with variations in more than one gene. The
process of obtaining informed consent for genetic tests related to
a multifactorial or polygenic clinical outcome is particularly
difficult since it requires the practitioner to instruct the
individual in the action of multiple genes singularly and together
as well as non-genetic or environmental factors that contribute to
such a clinical outcome and how such non-genetic or environmental
factors may be modified to alter the course or incidence of the
clinical outcome. It is recognized that genetic tests are often
most useful for multifactorial clinical outcomes since the
identification of genetic risk factors for a clinical outcome may
enable modification of complementary non-genetic or environmental
risk factors that may alter the course or incidence of that
clinical outcome. In specific embodiments of this invention relate
to tests for genes associated with multifactorial or polygenic
clinical outcomes where such outcome is associated with one gene,
two genes where such genes are related members of a gene family, a
pathway, process or clinical outcome, three such genes, five such
genes, more than five such genes, more than ten such genes, or more
than 100 such genes. A specific embodiment of this invention is an
instrument for obtaining informed consent for genetic tests one
gene, two genes where such genes are related members of a gene
family, a pathway, process or clinical outcome, three such genes,
five such genes, more than five such genes, more than ten such
genes, or more than 100 such genes. In a specific embodiment of
this invention is an instrument for obtaining informed consent for
a genetic test that is a gene screen for two or more than two genes
that may not be related, specifically more than 10 genes, more than
100 genes, more than 1000 genes, or more than 10,000 genes.
Those skilled in the art recognize that often all of the genes and
variations that are related to a clinical outcome may not yet be
known. Genetic tests for variations in known genes are often useful
in identifying risk factors for clinical outcomes. As the number of
genes that are known within the human genome increases as a result
of genomic research, and as further genomic research ascribes
specific functions to these genes in health and disease and
identifies variances within these genes that are associated with
clinical outcomes, it will be desirable to perform additional
genetic tests to further refine the assessment of risk. If DNA
banking is performed when the initial sample is obtained, it is
often possible to use this sample for such additional tests. A
specific embodiment of this invention is an instrument for
obtaining informed consent for a genetic test for more than one
gene, related genes, a clinical outcome, or a gene screen which
authorizes DNA banking and additional genetic tests for related
genes at a future time. In specific embodiments, informed consent
is obtained for such tests with notification or assent of the
individual.
"Genetic risk" is a quantitative and/or statistical measure of the
likelihood that an individual will have a clinical outcome as a
result of variations in one or more than one gene. The risk may be
expressed, for example, as the fold increase in risk of a
particular clinical outcome, the likelihood or probability that an
individual will experience a particular clinical outcome, or an
odds ratio. Various methods for determining these measures are
known by those of ordinary skill in the art and are commonly
described in medical journals in conjunction with the discovery of
genes that are considered risk factors for specific disease and in
textbooks of medicine and genetics. Risk is often described as a
statistical range which describes the probability of an individual
experiencing a clinical outcome, for example risks being <10%,
10-25%, 25-50%, 50-75%, 75-90% or >90%. Risk may also be
determined as a fold increase in risk, for example and individual
may have a a <2, 2-5, 5-10, or >10 fold increased likelihood
of a clinical outcome if they have a certain genetic variation. A
gene or sequence variation in a gene is a "risk factor" for a
specific clinical outcome, condition and/or disease if the gene or
variation is associated with a change in the risk or likelihood of
that outcome.
"Genetic risk", susceptibility", "predisposition", and "risk" are
often used interchangeably to describe the likelihood of a
individual exhibiting a disease, disorder, or clinical outcome. It
is recognized that a risk factor may refer equally to variations
that increase the risk of a specific outcome or to variances that
reduce the risk of that outcome. The determination of genetic risk
often makes use of data from a medical and family history in
addition to data describing the test result. The presence or
absence of a specific variation or gene may have greater predictive
value based on the family history of a specific clinical outcome
and specific pattern of inheritance in that family.
The methods used to determine genetic risk as well as the
statistical significance, sensitivity, specificity, and the
predictive value of such information is described to the individual
as part of the process of obtaining informed consent. The
predictive value of a specific test may be described as the
relative contribution of a specific variance or gene to a clinical
outcome or to the fraction of individuals with a clinical outcome
in which such outcome is attributable to a specific variance or
gene. Studies suggest that the perceived accuracy of a test is
particularly important to individuals who are considering whether
or not to have a test performed. A description of factors including
the technical specifications for the test (e.g. false positives and
false negatives associated with the laboratory procedure), the
statistical significance, specificity, and sensitivity of the
association between a variance or gene and a clinical outcome, and
the predictive value of the test result all contribute to the
perceived accuracy of the test. While such information is available
to those skilled in the art in reports describing the association
of a specific variance or gene with a clinical outcome, it is
difficult for many practitioners who are not skilled in genetics to
ascertain such information and describe this information to
individuals. A specific embodiment of this invention is an
instrument for obtaining informed consent containing an integrated
instruction element which describes the calculations for
determining an individual risk based on the results of said tests,
statistical processes (including the significance, sensitivity, and
predictive value of the test results), personal medical history,
and family history. In a specific embodiment the instrument
contains stepwise instructions or a worksheet for the practitioner
to determine an individual's risk.
The term "medical history" is well known in the art. The term
"family history" or "family medical history" refers to information
on the health of an individual's relatives, diseases they may have
suffered, and the cause of death attributed to deceased family
members. An individual who undergoes a genetic test is often
referred to as a "proband". A family history is most commonly
obtained by asking an individual about their relatives and is
commonly presented as a family tree illustrating the family
relationships and notes about their medical history. A family
history may be obtained using computer programs such as
TreeBuilder.TM. or Cyrillic.TM.. Certain tests may have limited
predictive value in the absence of a family history of a specific
clinical outcome. Other tests may have greater predictive value if
the family history is known. When genetic tests are performed for
the purpose of reproductive counseling, the family history will
also contain information about an individual's reproductive
partner, for example a spouse, partner, or egg or sperm donor, and
their related family members.
The term "family members" includes family members of the proband as
well as family members of a reproductive partner. As part of the
informed consent process, it is often important to collect an
individual's medical history and family history to help the
individual assess the potential predictive value of the test. A
specific embodiment of this invention is an instrument for
obtaining informed consent for one, or more than one, genetic test
which includes collection of information on an individual's medical
history or family history. A specific embodiment of this invention
is an instrument for obtaining informed consent for one, or more
than one, genetic test, containing an integrated collection element
which directs the practitioner how to determine an individual's
risk based on the individual medical history, family history, and
results of said test. In a specific embodiment the instrument
contains stepwise instructions or a worksheet for the practitioner
to determine an individual's risk based on the medical history or
family history. A specific embodiment of this invention is a
computer program for collecting an individual's medical history or
family history integrated with an instrument for obtaining informed
consent.
Several medical organizations such as the National Institutes of
Health, the American College of Human Genetics, and others
promulgate "recommendations" on the use of genetic tests that are
often based on the prevalence of a clinical outcome in a specific
population or demographic group or a family history of a clinical
outcome. Such recommendations are often based on the predictive
value of the test and it's potential effects on an individual's
quality of life, the prevalence of disease in a population or
demographic group and it's potential impact on health care
economics (pharmacoeconomics). Such recommendations do not prohibit
the use of genetic tests by an individual, though they may have a
role in decisions concerning reimbursement for such tests. An
important part of the process of obtaining informed consent is to
instruct an individual concerning recommendations that are relevant
to the test being considered and an assessment of whether the
individual meets the criteria for the test and whether such
recommendations are relevant to the individuals concerns. A
specific embodiment of this invention is an instrument for
obtaining informed consent for a genetic test or more than one
genetic test which describes recommendations to concerning such
tests and guides the practitioner in an assessment of the
recommended course of action for the individual. A specific
embodiment of this invention is an instrument that guides the
practitioner to instruct individuals concerning recommendations
concerning genetic testing.
An exemplary purpose for performing a genetic test on an individual
is to establish an measure of an individual's risk of a specific
clinical outcome using a genetic test to determine the sequence of
one gene, more than one gene, related or unrelated genes, or a gene
screen in the sample, the presence or absence of one, or more than
one, sequence variation genetic marker, variance, variation,
mutation, polymorphism, or micro satellite sequence associated with
one gene or more than one genes, the presence of one, or more than
one, viral sequence, viral-like sequence, or repetitive sequence, a
haplotype or genotype spanning one gene, or more than one gene,
related genes, the number of copies of one or more than one gene,
the amount or characteristics of RNA or protein expressed from one,
or more than one, gene, the biological function of one, or more
than one, gene, the arrangement of genes within the genome, the
chromosome number, or integrity of chromosomes.
This invention preferably concerns genetic tests useful in medicine
that identify associations with a clinical outcome such as a
health, genetic disease, multifactorial diseases, or an
individual's response to therapeutic drugs. Such associations are
generally established through clinical trials which collect data
both on the clinical outcome and genetic variations in a sample
obtained from the individual. It is often necessary to perform
multiple clinical trials to achieve a consensus on the significance
of a specific variation on an individual's genetic risk of a
specific clinical outcome. Methods for performing such studies are
known to those skilled in the art, and the results of such studies
are commonly reported in publications in the medical literature and
presentations at scientific meetings.
Initial reports of genetic tests may involve studies on small
populations which demonstrate the statistical association of a gene
or sequence variation with a clinical outcome. Such studies may
suggest that a test has potential utility. These data must then be
supplemented by additional studies which confirm and refine the
accuracy of this observation and establish the utility of the test
in quantitatively determining the genetic risk of a clinical
outcome. Sometimes it is necessary to perform many studies or
perform meta-analyses which combine the data from several different
trials to establish that a test is useful in determining the
genetic risk of a clinical outcome. Studies performed as part of
the research and development of a genetic test are commonly
described in reports in scientific and medical journals,
presentations at scientific meetings, and, sometimes, in filings
made to regulatory authorities to obtain authorization for
manufacture or sale of a diagnostic product designed for use in
performing a genetic test. Once a genetic test has been validated
through multiple clinical studies, information about such tests
will be found in textbooks of medicine, genetics or clinical
pathology, in materials for medical education and continuing
medical education. Once a diagnostic product is approved by the FDA
or offered by a certified testing laboratory, additional
information is often available from the manufacturers of a
diagnostic product or laboratories that perform the test on a
commercial basis. More than 500 validated tests for variations in
specific genes have been described and are performed by certified
laboratories. Information on tests that are commonly performed in
clinical practice is available to those skilled in the art, for
example through the Internet locations genetest.org and
geneclinics.org, textbooks such as Scriver et al., The Molecular
Basis of Inherited Disease, McGraw Hill, databases available
through the internet location nhgri.nih.gov, the National Center
for Biological Information (NCBI) linked to the human genome
project, and through academic journals of medicine and related
sciences indexed through MEDLINE. New genetic tests are being
discovered at a rapid rate due to continuing progress of the human
genome project and associated clinical research. Those skilled in
the art recognize that it is difficult to remain current on the
many reports describing basic genetic research and clinical trials
on genetic tests and their application to determine the genetic
risk of many different clinical outcomes. Information from such
reports is important both to the practitioner who must describe the
test to the individual, and to the individual who must decide
whether or not to have the test performed. Moreover, it is often
difficult to describe medical studies in simple language that is
generally understandable by individuals. A specific embodiment of
this invention is an instrument for obtaining informed consent for
one genetic test or more than one genetic test with an integrated
instruction element which provides the practitioner with a current
summary of information from reports concerning such test or tests
as well as illustrative materials which facilitate the instruction
of an individual concerning such tests at an appropriate level of
comprehension. In a further embodiment this information is
incorporated in an information element for individuals with text
and illustrative materials at a level appropriate for
individuals.
The invention provides instruments and methods for obtaining
informed consent comprising validated elements with information
concerning the genetic test, elements for instructing an individual
concerning the genetic test, elements for collection of personal
medical history and family history, elements for assessing the
individual's retention and comprehension of information, and
elements for certification of informed consent. These methods and
instruments enable practitioners and individuals to obtain a
meaningful and legal informed consent.
"Informed consent" or "consent" mean the process by which
individuals receive information about a genetic test, are informed
of the potential benefits and risks associated with performing a
genetic test, and provide legally binding permission for such a
test to be performed on their provided sample. The terms informed
consent or consent also mean the legally binding consent provided
by an individual or a document, the "informed consent document",
executed by an individual which certifies their consent for a
genetic test to be performed. "Assent" means the process by which
an individual indicates their acceptance of a genetic test without
providing a legally binding consent. For example, minors generally
are considered incapable of providing a legally binding consent,
but may provide assent. Standards of medical care and some state
laws require that an individual provide an informed consent for a
genetic test to be performed.
The elements of a document for certifying individual's consent and
guidelines for what constitute an informed consent process and
legally binding informed consent document are known in the art.
Informed consent for genetic testing often resembles the consents
obtained for human subject research as described in the Code of
Federal Regulations in sections 46.116 and 46.117. These guidelines
are formally applicable only to tests that are performed for
research purposes and are not formally applicable to the consents
required for validated genetic tests that are performed for the
purpose of determining and individuals risk of a clinical outcome.
Nevertheless, many informed consents used for genetic testing
retain the elements of an informed consent for research purposes,
in part because many genetic tests are not yet fully validated and
may be considered by some to be research even though they are
performed primarily for diagnostic purposes. Also, informed consent
standards for research have been retained for genetic testing
because many institutions seek consent to use samples and banked
DNA that are obtained for diagnostic purposes for research purposes
as well. An embodiment of this invention is an instrument which
provides for an informed consent for genetic in compliance with
Code of Federal Regulations in sections 46.116 and 46.117. An
exemplary use of such consents would be for genetic tests performed
for research purposes.
Other informed consents for genetic testing resemble the legal
consents used for medical procedures such as surgery. The
principles underlying such consents are primarily matters of state
law and legal doctrine arising from common law (judicial decisions)
as it applies to decisions about medical treatment and procedures.
The operable standard under this doctrine is that the practitioner
must disclose information that is or would be material to the
patient in making his or her decision and information that a
reasonable practitioner in similar circumstances would disclose.
Some states in addition to the common law standard have carved out
specific rules (statutes) proscribing the process for informed
consent in regard to specific tests or procedures as well as the
content of the disclosures that must be made to the patient facing
those procedures. In some states genetic testing is treated this
exceptional way and there are specific statutes on genetic testing.
The statutes in most states are silent on the issue of informed
consent for genetic testing, leaving the common law standard as the
one that must usually be met. In the absence of a legal standard
governing informed consent for genetic testing, the burden is
increasingly placed on institutions and individual practitioners to
provide sufficient information and instruction and collect relevant
information sufficient to make the consent valid. As described
herein, this may include, for example, information about the
genetics, the genetic tests that will be performed, the use of
genetic results, the risks and benefits of performing a test,
recommendations concerning use of the genetic test, determinations
of genetic risk, the use of sample, and procedures for records and
protecting privacy. The preferred embodiment of this invention is
an instrument which provides for an informed consent which assures
compliance with statues concerning informed consent for genetic
tests. An exemplary use of such consent is to obtain consent for a
test performed using a diagnostic product, preferably a diagnostic
product approved by the FDA. Another exemplary use of such consent
is to obtain consent for a test performed by a certified reference
laboratory operating under CLIA regulations as a "home brew". A
preferred embodiment of this invention is an instrument that
provides for an informed consent for a genetic test that is not
research.
The inadequacy of current informed consent practices has been noted
in many reports in the medical literature. Major problems include
the inability of many practitioners to provide sufficient
information and instruction for the individual to make a truly
informed decision. Another problem is the difficulty of
communicating technically difficult information at a level
appropriate for most individuals. Another problem is the poor
retention of information and understanding of information required
to provide an informed consent by individuals.
"Individual" means any person who may provide consent for a genetic
test or have a genetic test performed. This includes individuals
who may provide consent for genetic tests performed on their own
samples, individuals with legal authority to authorize genetic
testing for others, for example parents who may provide consent for
genetic tests of a minor, and individuals who have tests performed
as a consequence of such consent.
"Practitioner", "provider", or "health care provider" are used
interchangeably and include, for example, practitioners specialized
in genetics with MD, PhD or MS degrees, genetic counselors,
practitioners of primary care, specialties or subspecialties
including physicians, nurses, physicians assistants, pharmacists,
social workers, psychologists, as well as other ancillary
healthcare professionals or non-professional personnel or their
designees and the medical practices, hospitals, managed care
organizations, or institutions for whom they are agents. The term
may also include specialists trained in alternative healthcare
practices including, for example, osteopaths or chiropaths. The
terms refer to any provider of health services who may legally
assist an individual in procuring a genetic test. The term
practitioner may also relate to automated systems established by,
or at the direction of, a practitioner that may be used to obtain
informed consent from an individual. In such instance the term
includes computer hardware and software or Internet sites that
carry out such functions. In certain instances the practitioner is
a virtual embodiment of the electronic medium and the instruction
element is a computer program that guides the individual through
the process of informed consent in an interactive manner. In some
instances the virtual provider may be represented by a program or
figure with synthetic voice and voice recognition systems.
"Record" or "recording" refers to a system, document, or file
containing medical data about an individual. The record may contain
an individual's identity and the results of genetic tests and also
information about personal and developmental history, medical
history, family history, clinical laboratory data, images, findings
on physical exam, and previous illnesses and therapies as well as
reference or links to other records. Those skilled in the art will
recognize that it is important to protect the privacy of genetic
records. Genetic privacy laws in many locales mandate extensive
protections for the privacy of genetic information. Methods for
protecting the privacy of records are known in the art and include
maintaining records in a secure environment, eliminating
identifiable information that can be used to associate an
individual with their record in favor of codes. Patient numbers and
passwords are exemplary codes. A specific embodiment of this
invention is an instrument for obtaining informed consent for a
genetic test or one or more genetic tests which incorporates
procedures for creating a record containing genetic information and
for protecting the privacy of said record. Those skilled in the art
recognize that individuals need to be informed about policies and
procedures used to maintain a record containing the results of a
genetic test and any other medical information or identifiable
information as part of the process of providing informed consent
for a genetic test. Individuals must be informed what steps will be
taken to protect privacy, who will be authorized to access this
information, and whether the information may be used for research
purposes. A specific embodiment of this invention is an instrument
for obtaining informed consent for a genetic test or one or more
genetic tests which describes procedures with regards to a record
containing genetic information and protections for individual
privacy.
A "test result" or "genetic test result" means the end result of a
genetic test including, for example, the sequence of one or more
genes within a sample, the presence or absence of one or more
genetic markers, variances, variations, mutations, polymorphisms,
or micro satellite sequences, the presence of one or more viral
sequences, viral-like sequence, or repetitive sequence, a haplotype
or genotype spanning one or more genes, the number of copies of one
or more genes, the amount or characteristics of RNA or protein
expressed from one or more genes the biological function of one or
more genes, the arrangement of one or more genes within the genome,
the chromosome number, or integrity of chromosomes together with
known associations of such findings with a specific clinical
outcome. Genetic test results may also include inferences or
statistical data from clinical trials which establish the
association of test results with a clinical outcome to provide an
assessment of genetic risk and may include a determination of
genetic risk based on the genetic test, medical history, family
history, and clinical data.
"Genetic counseling" or "counseling" means the process of providing
information to an individual concerning a genetic test or clinical
outcome associated with a genetic risk. It includes the process of
providing information to an individual concerning the use of a
genetic test or genetic test result. Counseling is recognized by
those skilled in the art to be an essential step in providing an
individual with an accurate assessment of their genetic risk and
providing an individual with assistance in the use of this
information in making decisions regarding healthcare, lifestyle,
family planning, reproductive counseling or other activities.
Counseling is generally performed by a practitioner who has
specialized training in genetics or in specific diseases.
Counseling generally occurs in a practitioner's office and involves
one or two sessions with a practitioner. Counseling can be
performed before a test is performed as part of the process of
obtaining informed consent and can also be performed after
obtaining the test results to aid the individual in understanding
their genetic risk and making effective use of this
information.
The process of genetic counseling is described in many articles and
textbooks. The process commonly includes collecting a personal
medical history or family history from an individual, discussing
the benefits and risks of a genetic test, communicating the results
of a genetic test, and explaining the medical significance of the
genetic test results, elaborating on various health related choices
the individual may make on the basis of the genetic test results,
and discussing the consequences of genetic test results to family
members, reproductive partners, or other individuals designated
physician. It is generally considered important for genetic
counseling to be "non-directive", meaning that information is
provided to an individual without value judgments or implied
direction concerning the decision to perform a genetic test and the
use of the test results. This is particularly important when
genetic tests can be used for reproductive decisions, particularly
decisions relating to pregnancy termination. When genetic testing
is performed for common diseases, counseling frequently is
concerned with the various treatment options or lifestyle
choices.
A critical aspect of genetic counseling is the ability to
communicate complex information about a clinical outcome, genetic
tests, genetic risk, and genetic test results in a way that it is
known to be understandable to most individuals. Genetic information
is very complex, and it is often difficult to communicate this
information to individuals who commonly have little technical
background or understanding of genetics. Such communications are
preferably at the 8.sup.th grade level of written comprehension. In
current practice, genetic testing is initiated by healthcare
practitioners. In some instances a prescription from a practitioner
is required for a certified laboratory to perform a test. A
specific embodiment of this invention is an instrument for
obtaining informed consent for a genetic test or one or more
genetic tests which also provides a mechanism by which the
practitioner can prescribe a genetic test.
A major limitation of current practice is that many healthcare
practitioners, particularly primary healthcare practitioners who
are in the best position to use genetic tests to assess an
individuals genetic risk or predisposition to diseases before they
occur, are not sufficiently familiar with the current literature on
genetic tests to provide individuals with information or
instruction, collect adequate family histories, or obtain a
meaningful and legal informed consent. Genetic counseling can be
obtained through a referral to a healthcare practitioner specially
trained specially in genetics. The genetics professional commonly
meets with the individual one or two times, and the responsibility
for ongoing medical care will continue to reside with the referring
practitioner. It not practical to refer all individuals to
practitioners specially trained in genomics. It is anticipated that
by 2006, 10-40 million tests will be performed annually. At the
present time there are <3,000 individuals with specialized
training in genetics. The instruments described in this invention
have utility in providing practitioners with the information and
instructions required to provide counseling to individuals
sufficient to obtain an informed consent.
Information about genetic risk is available from sources other than
healthcare practitioners. Patient support groups specializing in
certain disorders or classes of disorders are often an important
source of information for individuals. General information is also
available on the Internet or world wide web, for example at
Internet locations such as genetests.org, geneclinics.org, nih.gov,
rarediseases.org, genetichealth.com, dna.com and genesage. While
many individuals seek information from such sources, the quality
and relevance of the information varies widely and this information
is not integrated with the counseling provided by the practitioner
or the informed consent process.
Samples are generally obtained by the health care practitioner, a
central blood drawing service of a hospital or health care clinic,
or a satellite facility of a diagnostic testing service. Samples
can also be obtained by an individual, for example by using an
OraSure device. Samples are commonly sent to genetic testing
services, often referred to as reference laboratories for genetic
tests, such as Genzyme Genetics, Quest Diagnostics, LabCorp, or
Specialty Laboratories, certain clinical laboratories or hospital
based, or academic research laboratories. Such laboratories are
commonly regulated by Clinical Laboratory Improvement Act (CLIA)
which sets standards for the performance and reporting of test
results. Genetic tests are not currently regulated by the FDA
though, in the future, may be developed as FDA approved diagnostic
tests or kits for use by diagnostic laboratories or even home use.
Genetic tests available from a certified reference laboratory or
available as diagnostic kits are generally referred to as
validated, meaning they have been subject to clinical evaluations
and have demonstrated clinical utility. Such tests are
differentiated from those that are not yet validated and are
performed on a research basis. A preferred embodiment of this
invention relates to validated tests that are not covered by
guidelines governing clinical research. A separate embodiment of
this invention relates to tests that are designed as research where
the guidelines for informed consent must comply with sections
46.116 and 46.117.
"Validated" is known in the art and refers to the process by which
a method or an instrument is established in a reproducible fashion
and subjected to testing to establish its utility and validity. For
example, a clinical procedure or laboratory test is validated if it
is performed in a reproducible manner and is shown through research
to have clinical value. Methods or instruments are validated
through an iterative process of developing the text and materials
that comprise the instrument, and then testing these texts or
materials in a clinical study to determine whether they are
understandable. Texts or materials which are poorly understood by
study subjects are then revised and retested until a desired level
of comprehension is achieved in the study population. Larger
studies can then be performed to demonstrate the efficacy of the
entire instrument in achieving a desired level of retention and
comprehension in a borad population representing different ethnic,
demographic, or socioeconomic groups. Methods for validating an
instrument are known in the art and involve testing the instrument
on a sufficiently large number of people to perform a statistical
analysis on the data. A set of performance specifications are
establish concerning the retention and understanding of information
concerning the genetic test by the individual, the proper handling
of the sample and genetic information, and the satisfaction of both
the individual and the practitioner in the adequacy of the process.
Statistical analysis is performed to demonstrate that the
instrument adequately meets the performance specifications. In a
specific embodiment, the instruments described in this invention
are validated through clinical studies that demonstrate their
utility in providing information and counseling to individuals and
obtaining a valid informed consent. Use of a validated instrument
often involves training in the use of the instrument quality
controls designed to maintain consistency in the use of the method
or instrument, as well as quality assessment and process
improvements designed to maintain the quality of the method or
instrument, and work towards improvements in efficacy or
efficiency.
"Training" means curriculum and materials for instructing
practitioners in the use of the instruments and methods described
herein. This may involve specialized materials for use in medical
education, continuing medical education, or group or individualized
instruction of practitioners in the use of the instrument by those
skilled in the use of these instruments.
"Quality control" and "quality assessment" refer to the ongoing
process of measuring whether performance specifications are being
achieved through use of the instrument. Quality control is achieved
by integrating elements into the instrument that assess whether the
performance specifications are met and by implementing procedures
for review of these elements on an ongoing basis. Such review may
involve analyzing a random sample of results, results in selected
regions or populations based on the particular test being
performed, the specialty of the practitioner, or the health,
language, ethnic origin, or socioeconomic status of the
individual.
Validated instruments are known in the art, for example, for
neurocognitive testing. For examples tests such as the Wechsler
Individual Achievement Test (WIAT), Wechsler Adult Intelligence
Scale (WAIS), Boehm Test of Basic Concepts, California Verbal
Learning (CVLY-II), Kaplan Baycrest Neurocognitive Assessment,
Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Intelligence
Scale for Children (WISC-III), Bayley Scales of Infant Development
(II) and many other tests have been developed to test individuals
for neurological, developmental, and psychological performance and
achievement. Once developed these tests are subjected to clinical
evaluation to validate the reliability of the instrument.
Practitioners who administer these tests do so by purchasing
packages with the exam that are provided to the individual taking
the test, an instruction set that provides stepwise guidance on
performing the test, and a scoring sheet to score the individuals
answers and compute established performance parameters. Other
validated instruments are used to assess clinical depression such
as the Beck Depression Inventory (BDI), Depression Scale (DEPS),
Duke Anxiety Depression Scale (DADS), Hopkins System Checklist
(HSCL), Primary Care Evaluation of Mental Disorders (PHQ), and the
Symptom Driven Diagnostic System-Primary Care (SDDS-PC).
"Integrated" means elements that are linked in their content,
components, structure, sale, operation, or use. An instrument is
integrated if it comprises two or more than two integrated
elements. Elements are integrated if there is cross-reference
between the elements, coordinated text or illustrative materials
between the elements, or explicitly complementary functions in the
design, content, composition, materials, function, or intended use
of the elements. An example is an instruction element that guides
the practitioner through the process of providing information in an
information element to an individual, collecting a medical history
or a family history using a collection element, assessing the
individual's retention and comprehension of the information using
an assessment element and certifying their consent using a
certification element. Other examples of integration include
providing the practitioner with text or illustrative materials in
an instruction element that match or complement the information
provided directly to the individual in an information element,
providing the practitioner with instructions, in an instruction
element, for assessing, using an assessment element, an
individual's retention and understanding of the information in the
information element, and providing the practitioner with materials
for obtaining and labeling a sample or sample collection device,
creating a genetic record, or billing along with instruction in the
use of such materials.
A checklist is a useful component of an integrated instrument.
"Checklist" means a form in printed or electronic medium that lists
key steps involved in obtaining an informed consent using the
instrument which is designed such that the practitioner can confirm
when each step has been performed and/or completed. The checklist
can be used by the practitioner in practicing the method of
obtaining informed consent using the instrument, can be
incorporated in a medical record to document the method that was
used, and can be used for quality control of the method and
instrument. For example, the checklist may list contain entries
related to the description of the genes involved in a clinical
outcome, the genetic test, the nature of a specific clinical
outcome, the role of genetic tests and test results in managing a
clinical outcome, how genetic tests are performed, the nature and
purpose of informed consent, how samples are obtained and handled,
what happens to the sample after the test is performed, whether the
sample can be used for other purposes, whether the sample will be
available for additional tests in the future, who will perform the
test, who receives the test results, what information will be
placed in a medical or genetic record, how this information may be
used, policies for protecting the privacy, as well as other
information included in the information element or instruction
element. A specific embodiment of the method is use of a checklist
for obtaining informed consent using an integrated instrument.
Worksheets are also useful components of an integrated instrument.
"Worksheet" means a form in printed or electronic medium which is
used for the collection or processing of data. Worksheets are
typically designed to prompt the user to collect and record certain
data, for example by filling in the blanks on the form or providing
answers to specific questions. Worksheets can also guide the user
through a series of calculations by arranging data entries in a
convenient layout, providing additional data or data tables
necessary for the calculation, and indicating the mathematical
functions to be used. Worksheets are recognized to be useful in
obtaining a medical history, review of systems, and family history
by providing a list of specific symptoms, signs, diseases, or
clinical outcomes that should be addressed. Worksheets can be used
to calculate genetic risk based on a family history or a genetic
test result by providing a format for systematizing the data, the
calculations that need to be performed, and statistical tables.
The invention provides for the integration of elements for
obtaining informed consent including two, or more than two, or the
following: an information element, with information for individuals
concerning genetic tests, an instruction element for practitioners
to assist in providing information to the individual, obtaining an
informed consent, obtaining a sample, and establishing a record, a
collection instrument for obtaining an individuals medical history
and family medical history, an assessment element to assess the
individual's retention and comprehension of information, a
certification element for certifying an individual informed
consent, as well as elements for obtaining and labeling the sample,
creating a genetic record, and billing. A specific embodiment of
this invention is the integration of the elements required to
obtain a valid informed consent into an instrument that may be used
by a practitioner to obtain informed consent from an
individual.
Integration is achieved by development of elements designed to be
used in a coordinated fashion. For example, it may first be
determined by experts what information an individual should receive
and what information they should retain and understand in order to
provide a valid informed consent. An information element for the
individual may then be developed along with an element for
assessment that would ascertain whether an individual retained and
understood this information. An instruction element may then be
developed as a teaching guide for the practitioner through the
process of obtaining consent. These elements may then be subjected
to validation to determine whether use of the instruction element
and information element, in fact, provides most individuals with
the requisite information to provide consent. Several iterations
may be required in the development of these integrated elements to
achieve the performance specifications. Integration is also
achieved by providing the practitioner with all of the elements
required to complete the process of achieving informed consent,
create a medical record, and processing a genetic test. Integration
may also be achieved by providing different elements required to
obtain informed consent and process a sample together, for example
in the form of a booklet or package that contains several elements.
Integration may also be achieved in the design of the elements such
that entries made in one element are systematically incorporated in
another element, for example through the use of carbon copies. Such
integration has utility both in improving the efficiency and
quality of the informed consent process.
"Electronic medium" are known in the art and the term refers,
without limitation, to software and hardware capable of carrying
out the unique methods and embodiments described herein including
the computer code, concept, content, components, design,
construction, appearance, look, feel, animation, text, graphics,
organization, storage systems, presentation systems, and function
of the medium. In an embodiment of this invention, the electronic
medium are interactive such that the individual or the practitioner
may direct or query the system. In an embodiment of the present
invention, such electronic medium contains synthetic speech and
speech recognition capabilities.
The terms "printed medium" or "printed materials" are generally
known in the art and refer, without limitation, to text or
illustrative materials on paper in bound or unbound form, boards,
labels, transparencies, photographs, or objects as well as the
concept, content, components, design, construction, appearance,
look, feel, figures, graphics, and organization of the materials.
In a preferred embodiment of this invention the instrument
comprises elements in printed medium that can be separated.
"Carbon copy" refers to the imprinting of entries made by a
practitioner or individual on multiple pages of the instrument
simultaneously, for example through the use of carbon paper or
other paper or materials designed for that purpose. Carbon copy
also refers to the copying of information entered into one element
through electronic means to other integrated elements within the
instrument, for example by copying into another element in
electronic medium or through the printing into a printed medium. In
a preferred embodiment of this invention, the printed materials are
constructed such that a carbon copy of information entries in one
element are copied on other integrated elements.
"Text" is known in the art and means written materials whether in
printed or electronic form including associated images, diagrams,
or pictures. "Illustrative materials" means materials designed to
assist the instruction of the individual and promote understanding
and retention of the information. Illustrative materials may
include, without limitation, diagrams, pictures, photographs,
poster, displays, exercises, models, objects, games, props, or
worksheets. Illustrative materials may be in the form of printed
medium or electronic medium and may include various objects. For
example, diagrams showing different patterns of inheritance may aid
the understanding of the role of inheritance of a particular gene
or the inheritance of clinical outcome. Photographs or models may
aid the understanding of a clinical outcome. Exercises, games, or
worksheets may aid the comprehension and retention of information.
An "object" may be used to illustrate principles of genetics, for
example the use of dice to illustrate principles of chance and
probability.
This invention comprises printed materials with text and
illustrative materials for carrying out the unique methods and
embodiments described herein. Preferably, the invention is in the
form of a booklet with printed materials comprising each of the
elements bound in such a way that the elements are integrated. For
example, a checklist within the instruction element can be used by
the practitioner and then incorporated in the recording element,
answers to questions in the assessment element or the certification
on the certification element can be marked by the individual and
incorporated in the recording element, and information in the
labeling element and billing element can be incorporated in the
recording element. Preferably this is achieved through the design
of the instrument such that a carbon copy of entries in one or more
elements is also made in the recording element when the initial
entry is made in the other elements of the booklet. Preferably also
the invention is in the form of a booklet with printed materials
comprising two or more elements bound in such a way that the
elements can be separated. For example, the information element may
be separated and provided to the individual, various illustrative
materials may be separated for use in instruction of the
individual, the recording element can be separated for
incorporation in an individual's general medical record, the label
element may be separated and affixed to a sample collection device,
and the billing element may be separated for processing by a
billing office. This is achieved through the design of the
instrument using methods known in the art such that pages are bound
together with certain pages perforated so as to enable easy
separation of selected pages from the other pages of the
instrument, or certain pages are affixed by adhesives which provide
for clean separation of one or more pages from the instrument. For
example, the information element may comprise a booklet that can be
provided to the individual and retained for their information. For
example, elements for assessment, certification, records, labeling,
and billing, may comprise separate pages that can be separated from
the instrument, and illustrative materials may be separated for
display on a board. In one embodiment, the pages or printing of
different elements within the instrument are color coded for
efficient separation. In alternative embodiment, the different
elements are distinguished by size of the page for efficient
separation. The instrument may be a kit containing different
printed materials including text, illustrative materials or objects
in a single package that can be separated for use by the individual
and practitioner.
Alternatively, this invention comprises electronic medium capable
of carrying out the unique methods and embodiments described
herein. This is achieved through the design and development of
computer programs wherein the different elements are presented to
the individual or practitioner as different pages on a computer
screen, windows, or pages printed by the computer program.
Preferably, the elements are integrated through the use of a menu
or, more preferably, links between the elements. The elements are
also preferably linked by the copying of information entered into
one element into one or more integrated elements. For example, the
information element may be linked to the assessment element so that
the individual can answer questions about the information which is
provided and return to review the information if necessary. The
instrument may be accessible via the Internet or loaded on a
specific computer. Methods are well known to those in the art for
constructing such functioning systems using HTML or JAVA.
The instrument may contain elements comprising printed materials
and elements comprising electronic medium. For example, the
information element may be an audio tape, video tape or interactive
computer system, while the elements for certification, labeling, or
records are printed materials. Alternatively, the information
element may be a pamphlet, while other elements of the instrument
are in electronic medium. Preferably, the electronic medium is
designed such that certain elements can be printed from the
program. For example, the information element may be printed for
the individual's records and the recording element, labeling
element, or billing element can be printed for use by the
practitioner.
The elements of the invention may be in any language, for example,
English, Spanish, French, German, Italian, Russian, Japanese,
Chinese, or Hebrew. Preferred are elements which use the primary
language of the individual. When the primary language of the
individual is different than the primary language of the
practitioner, certain elements may be in the language of the
individual and other elements in the language of the practitioner.
For example, the information element, collection element,
assessment element, and certification element may be in the primary
language of the individual, while the instruction element,
assessment element, recording element, billing element are in the
primary language of the practitioner. In further embodiments, the
instrument integrates translations for the practitioner of elements
that are in the primary language of the individual within the
element. One or more of the elements of the instrument or
components thereof may be in Braille or in oral form (e.g.
audiotape, videotape, or electronic systems with synthetic or
recorded voices) for those who are visually impaired or otherwise
unable to read printed materials.
B. Detailed Description of the Elements
This invention describes integrated instruments and methods with
utility in obtaining informed consent for genetic tests. The
instruments described in this invention comprise the following
integrated elements: (a) an information element for an individual
concerning a genetic test for one gene, more than one gene, related
genes, a clinical outcome or a gene screen; (b) an instruction
element for the practitioner useful in providing instruction to the
individual and guidance in the use of the instrument and obtaining
informed consent; and (c) a certification element, which can be
used to certify the individual's consent for the test.
The instrument of the invention may optionally include any one or
more than one of the following additional elements:
a collection instrument for collection of information concerning
the individual's personal medical history or their family medical
history;
an assessment element for assessment of the individuals retention
or comprehension of the information;
a labeling element for labeling a sample or sample collection
devise or diagnostic used for genetic testing with the identity of
the individual;
a billing element for payment by the individual or through a
reimbursement agency
a recording element that can constitute or be incorporated in an
individual's medical record;
a training element for training the instructor in the use of the
instrument;
a quality control element for monitoring performance of the
practitioner and the performance of the instrument; and
an indemnification element that can constitute an agreement to
indemnify the practitioner.
In a preferred embodiment the instrument comprises in an integrated
manner the information, instruction, certification and assessment
elements. In an alternative preferred embodiment the instrument
comprises in an integrated manner the information, instruction,
certification and collection elements. In another preferred
embodiment, the instrument comprises in an integrated manner the
information, instruction, certification, collection and assessment
elements. In yet another preferred embodiment, the instrument
comprises in an integrated manner the information, instruction,
certification, collection and assessment elements and at least one
of the elements selected from the group consisting of a labeling
element, a billing element, a recording element, training element,
a quality control element, and an indemnification element.
Alternatively, the instruments described in this invention
comprises the information, instruction and certification elements
and two, or more than two, or the following: a collection element,
an assessment element, a labeling element, a billing element, a
recording element, a training element, a quality control element,
and an indemnification element. More specifically, the instruments
described in this invention may comprise the information,
instruction and certification elements and two, three, four, five,
six, seven, or eight of the other elements described herein.
The elements comprising the invention may be integrated
individually in a pair wise manner or in groups within the
instrument, or, in alternative embodiments of the invention, the
instruments may be comprised selectively of such integrated
elements. For example, the information element may be integrated
with one or more of the following elements: an instruction element,
a collection element, an assessment element, a certification
element, a labeling element, a billing element, a recording
element, and a training element. Specifically, the information
element may be integrated with the instruction element, a
certification element, or an assessment element or all three of
said elements. Alternatively, the information element may be
integrated with the instruction element, a certification element,
or a training element or all three of said elements.
In another example, the instruction element may be integrated with
one or more than one of the following elements: an information
element, a collection element, an assessment element, a
certification element, a labeling element, a billing element, a
recording element, and a training element. Specifically, the
instruction element may be integrated with a certification or
assessment elements. The information and instruction elements may
be integrated with one or more than one of the following elements:
an assessment element, a collection element, a certification
element, a labeling element, a billing element, a recording
element, and a training element. Alternatively, the instruction
element may be integrated with an assessment element and one or
more than one of the following elements: an information element, a
collection element, a certification element, a labeling element, a
billing element, a recording element, and a training element.
Alternatively, the instruction element may be integrated with a
certification element and one or more than one of the following
elements: an information element, a collection element, an
assessment element, a labeling element, a billing element, a
recording element, or a training element. Specifically, the
instrument may contain an instruction element integrated with a
training element. Alternatively, the instrument may contain an
instruction element integrated with a training element and one or
more than one of the following elements: an information element, a
collection element, a certification element, an assessment element,
a labeling element, a billing element, or a recording element.
Specifically, the instrument may contain an instruction element
integrated with information and assessment elements. Alternatively,
the instrument may contain an instruction element integrated with
information, assessment, and certification elements. Alternatively,
the instrument may contain an instruction element integrated with
certification and training elements.
In another example, the instrument may contain a certification
element integrated with one or more than one of the following
elements: an information element, an instruction element, a
collection element, an assessment element, a labeling element, a
billing element, a recording element, or a training element.
Specifically, the instrument may contain a certification element
integrated with an assessment element. Alternatively, the
instrument may contain a certification element integrated with an
assessment element and one or more than one of the following
elements: an instruction element, an information element, a
collection element, a certification element, a labeling element, a
billing element, a recording element, and a training element.
Specifically, the certification element may be integrated with a
recording element. Alternatively, the certification element and
recording element may be integrated with one or more of the
following elements: an information element, an instruction element,
a collection element, a labeling element, a billing element, and a
training element.
In another example, the instrument may contain a training element
integrated with one or more of the following elements; an
information element, an instruction element, a collection element,
an assessment element, a certification element, a labeling element,
a billing element, and a recording element. Specifically, the
instrument may contain a training element integrated with an
instruction element.
The instrument may be used to obtain informed consent for a genetic
test for one gene. Alternatively, the instrument may be used to
obtain informed consent for a genetic test for more than one gene,
related genes or for genes associated with a clinical outcome. The
instrument may also be used to obtain informed consent for a gene
screen test.
The information element comprises text and illustrative materials
intended to provide an individual with sufficient knowledge about a
genetic test, the potential medical consequences of a genetic test,
and the procedures involved in genetic testing to provide a
meaningful and legal informed consent. The information element is
integrated with one or more other elements of the instrument. The
type of information required for an individual to provide a valid
informed consent is known in the art and disclosed in various
textbooks and publications in scientific journals as well as in
courses and presentations by individuals recognized to be opinion
leaders in the field. The information element provides such
information in the form of text and illustrative materials. The
text and illustrative materials include information about a
specific clinical outcome, the genes that constitute risk factors
for that clinical outcome, the significance of different genes that
constitute risk factors for that clinical outcome, the potential
actions that could be taken to prevent or treat the clinical
outcome based on genetic test results, how genetic tests are
performed, the purpose of informed consent, the process of
obtaining informed consent, how samples are obtained and handled,
the significance and process of DNA banking, what happens to the
sample after the test is performed, what happens to banked DNA,
whether the sample can be used for other purposes, whether the same
will be available for additional tests in the future, who will
perform the test, who will receive the test results, what
information will be placed in a medical or genetic record, how this
information may be used, policies for protecting the privacy and
confidentiality of test results, the availability, nature and role
of genetic counseling, factors which should be considered in
deciding whether to have a genetic test including the benefits and
risks of a genetic test, potential uses of test results in health
and wellness management and lifestyle decisions, the recommendation
of professional organizations. The information element may also
describe in the form of text and illustrative materials the
liabilities of various parties that may be involved in providing
information, handling the sample, performing the test results, or
providing the individual with guidance on the use of the test
results. The information element may also have background
information about genetics to aid understanding of genetic testing
in general, references (for example, books, publications, web
sites) to more detailed information, and contacts (for example, the
names, telephone numbers or web addresses of organizations or
individuals) who the individual can contact if they wish further
information. In a specific preferred embodiment, the information
element is validated.
The text and illustrative materials are designed for individuals
with an 8.sup.th grade education or level of reading comprehension.
Methods for assessing the grade level of language used in such an
element are known in the art. Optionally, the integrated instrument
may contain information elements at different grade levels or links
or references to advanced information for individuals who have the
interest and ability to comprehend such information and the
practitioner will select an information element with an appropriate
level of complexity for the individual. For example, text and
illustrative materials may be provided for individuals at the
8.sup.th grade level, 12.sup.th grade level, college students,
college graduates, or postgraduate level. Information can be
provided in any language, preferably the primary language of the
individual. Alternatively, information can be provided orally by an
audiotape, videotape, or computer for individuals who may be
illiterate.
In a specific embodiment, the text and illustrative materials
comprise printed material. Preferably the text and illustrative
materials can be physically separated from the other elements and
provided to the individual for their review or study. In an
alternative embodiment, text and illustrative materials comprise
electronic medium. In an embodiment, the instruction element may be
a video that provides information to the individual or an audiotape
linked to illustrative materials. In a specific embodiment, the
text and illustrative materials are on the Internet or computer. In
another alternative embodiment, the text and illustrative materials
are comprised of a combination of printed materials, electronic
medium, and/or objects.
The instruction element comprises text and illustrative materials
intended to assist a practitioner in the use of the elements that
comprise the instrument. The text and instructional materials
contain instructions for the practitioner on use of the instrument,
instructions for to be provided by the practitioner to the
individual on the use of the instrument and the process of
providing informed consent, instructional materials to guide
discussion with the individual concerning a genetic test for one
gene, more than one gene, related genes, a clinical outcome, or a
gene screen, the nature of a specific clinical outcome, and how to
prevent or manage a clinical outcome including the role of genetic
tests and test results, the genes that constitute risk factors for
that clinical outcome, the significance of different genes that
constitute risk factors for that clinical outcome, the potential
actions that could be taken to prevent or treat the clinical
outcome based on genetic test results. The text and illustrative
materials also contain to instructional materials to guide a
discussion with the individual concerning how genetic tests are
performed, including the nature and purpose of informed consent,
how samples are obtained and handled, what happens to the sample
after the test is performed, whether the sample can be used for
other purposes, whether the sample will be available for additional
tests in the future, who will perform the test, who receives the
test results, what information will be placed in a medical or
genetic record, how this information may be used, policies for
protecting the privacy and confidentiality of test results, the
availability, nature and role of genetic counseling, instruction
guiding the individual's choice whether or not to perform a test,
potential uses of test results in health and wellness management
and lifestyle decisions, the recommendation of professional
organizations. instructions for using the element for assessment
including answers to the questions and instructions to determine
whether the individual demonstrates a minimum adequate level of
understanding, instructions for completing informed consent,
instructions for obtaining sample, instructions for labeling
sample, instructions for completing medical record, additional
background information on patterns of inheritance, genes, DNA,
chromosomes, specific clinical outcomes, psychosocial issues in
genetic testing, the potential for genetic discrimination, and
answers to frequently asked questions. The text and illustrative
materials in the instruction element are integrated with those in
the information element in that the text and illustrative materials
in each element may be "overlapping", i.e., one or more portions of
the text and/or illustrative materials in the instruction element
may be quoted in, recapitulated in, or similar in wording or
meaning, to a corresponding text and/or illustrative material in
the information element. The instruction element is intended for
use by the practitioner in helping individuals understand and
retain the information in the information element. The instruction
element can be in any language, most preferably the primary
language of the practitioner.
The instruction elements also direct the practitioner in how to,
inter alia, (a) provide information to an individual concerning one
or more than one genetic tests; (b) collect information concerning
the individual's personal medical history or their family medical
history; (c) perform an assessment the individual's retention or
comprehension of said information; (d) obtain certification of the
individual's consent for said test; (e) obtain a sample for
testing; (f) properly label the sample; (g) deliver the sample to
the appropriate laboratory for the test to be performed; (h) bill
the individual either directly or through a reimbursement agency
and (i) add appropriate information to the individual's medical
record. Preferred embodiments provide the instructions in a
stepwise manner.
In a preferred embodiment, the instruction element contains a
checklist, and in an embodiment of the method, the practitioner
uses a checklist to document the steps in obtaining the informed
consent. In a preferred embodiment the instruction element contains
specific language designed to ensure standardization and quality of
the informed consent to be used by the practitioner to instruct the
individual. The checklist contains items to be discussed with the
individual and contains the steps that comprise the method for use
of the instrument. In a preferred embodiment of the method, the
practitioner uses the checklist and integrated elements in
obtaining informed consent. In a specific embodiment, the
instruction element is validated.
The text or illustrative materials comprising the instruction
element describe the test to be performed, the potential test
results, the medical significance of potential test results as well
as choices that an individual may be able to make based on the test
results. The instruction element may also provide general
background information about genetics to aid understanding of
genetic testing by the individual. The instruction element may
describe specific benefits and risks of performing the tests and
recommendations concerning such the use of such tests. The text
and/or illustrative materials may describe the procedure for
obtaining a sample and performing a test, the disposition and
potential future use of the sample as well as the test results,
guidelines for protecting the privacy and confidentiality of the
individual, procedures for banking DNA, restriction on the use of
banked DNA, as well as legal boundaries concerning the liability of
various parties that may be involved in providing information,
handling the sample, performing the test results, or providing the
individual with guidance on the use of the test results. The text
and/or illustrative materials comprising the instruction element
may also provide stepwise direction on how to collect a personal
medical history or a family medical history, preferably using an
integrated collection element. In a preferred embodiment, the
instruction element includes text, methodology and illustrative
materials that teach the practitioner how to use the information
collected in the collection element. More preferably the
instruction element comprises a worksheet that enables the
practitioner to assess the significance of the personal medical
history or family medical history, for example, by calculating the
risk of a specific genetic disorder based on the number of affected
family members. In a preferred embodiment, the instruction element
includes text for calculating genetic risks based on the family
history. In a further embodiment, the instruction element may
comprise a worksheet or computer program that enables a calculation
of genetic risk based on family history.
In a preferred embodiment in which an assessment element is
included in the instrument, the instruction element directs the
practitioner through an assessment of the individual retention or
comprehension. In such embodiments, the assessment element contains
text comprising a series of questions to be asked by the
practitioner in assessing the individual's retention or
comprehension of the information and a corresponding answer set. In
an alternative embodiment, the element for assessment comprises a
series of questions in the form of a questionnaire that can be
completed by the individual, and the instruction element directs
the practitioner in how to administer the questionnaire and
provides correct answers to these questions as well as guidelines
for responding to correct and incorrect answers.
In a specific embodiment of the present invention, the instruction
element is printed material. In a preferred embodiment the
instruction element can be physically separated from the other
elements of the instrument and retained for use by the
practitioner. In an alternative embodiment the information element
is one element of an instrument comprising printed materials and
electronic medium. For example, the instruction element may be
printed material with directions on the use of a computer program
or web site that comprises the information element or other
elements of the instrument. In further embodiments the information
element is comprised, without limitation, of mixed medium including
printed materials, electronic medium, and objects.
In an alternative embodiment, the information element comprises
text and illustrative materials in electronic medium. In a specific
embodiment the instruction element is in electronic medium
comprised of text and illustrative materials that are used by the
practitioner to instruct the patient regarding the genetic test and
the use of the instrument. In a specific embodiment the
practitioner is a virtual embodiment of the electronic medium and
the instruction element is a computer program that guides the
individual directly through the process of informed consent in a
stepwise or interactive manner. For example, the instruction
element may be a computer program to present the individual with
information using the information element, perform an assessment of
the individual's retention and understanding using the assessment
element, create the record using the recording element, provide a
label for the sample using the labeling element, and arrange
payment using the billing element. The instruction element in
electronic medium may also provide the individual with direction on
the appropriate use of one or more of the elements, monitor the
progress of the individual through the informed consent process,
and provide additional information or directions as necessary to
assist in the effective completion of the informed consent process
and proper processing of the sample. In an embodiment, the
instruction element may be a computer program that instructs the
individual in the use of the instrument. In a specific embodiment,
the computer program may integrate the information element and the
instruction element. In an embodiment, the instruction element in
electronic medium may use an animated figure, photographic or video
image and/or a synthetic voice to represent a practitioner in
presenting information to the individual and/or instructions on the
use of the instrument. In a specific embodiment the electronic
medium employs synthetic voice and voice recognition systems.
The instruction element may contain objects that can be used by the
practitioner in presenting information to the individual. Objects
may include models, diagrams, or pictures of the human body or
disease states, for example, representations of the skeleton,
organs or tissues, "Games of chance" such as dice may be useful in
explaining the statistical nature of genetic risk and may be
incorporated as objects within the instruction element. These
objects may be integrated with the information element with text or
illustrative materials designed to demonstrate genetic
principles.
The certification element is a document that can be signed by an
individual to signify their consent for a genetic test to be
performed. This document resembles informed consent documents known
in the art and, by itself, is designed to comply with any legal or
statutory requirements for certification of informed consent. The
informed consent document comprising the certification element
summarizes the individual's understanding of the specific test that
will be performed, the benefits and risks involved, the procedure
for obtaining a sample and performing the test, the disposition and
potential future use of the sample and the test results, guidelines
for protecting the privacy and confidentiality of the individual
and their genetic information, and information concerning the
liability of parties involved in providing information, handling
the sample, performing the test, or providing the individual with
guidance on the use of the test results. The certification element
may also enable the individual to signify their consent for DNA
banking as well as stated uses of the banked DNA. The certification
element may also include the individual's consent to specific forms
of follow up, may indicate who should receive the test results and
how they want the results to be reported, may indicate whether they
are interested in receiving information with updates on research
about the genetic test, the test results, or new tests related to a
clinical outcome. The document contains blank signature lines for
execution by the individual, the practitioner, and at least one
witness. The certification element is integrated with other
elements of the instrument. In preferred embodiments, the
certification element is integrated with the information element
and instruction element. For example, the certification element may
recapitulate essential information from the information element or
may incorporate the summary of instruction provided to the
individual or a checklist from the instruction element. In another
preferred embodiment, the certification element is integrated with
the recording element. In further embodiments, the certification
element may be integrated with the assessment element, for example
by incorporating the results of the assessment. In a specific
embodiment, the certification element is validated.
The certification element comprises printed material that
preferably includes multiple execution copies or carbon copies so
that duplicate copes can be retained by the individual and
incorporated into the medical record, or provided to others who may
require certification of the individual's consent. In an
alternative embodiment, the certification element is in electronic
form and execution is by a legally recognized electronic signature.
In a preferred embodiment, the instrument is constructed such that
the signature entered into the certification element is directly
entered into other elements, for example the recording element or
the labeling element. The certification element may additionally
include a prescription to be issued by the practitioner, which
authorizes a testing laboratory to perform a test. Such
prescriptions for tests are required by certified laboratories in
certain states. In a preferred embodiment, certification element is
integrated with the labeling element such that the prescription
entered into the certification is copied on the label provided to
the laboratory with the sample.
The collection element comprises text and/or illustrative materials
useful in obtaining an individual's personal medical history or
their family medical history. Methods for obtaining personal
medical history are described in basic textbooks and clinical
manuals, and tools such as worksheets and computer programs are
well known in the art. Such texts and illustrative materials
contain questions about past illnesses as well as a "review of
systems" with questions concerning the health of various bodily
functions. Standardized instruments and methods for obtaining a
family medical history are also known in the art and involve the
cataloguing of information concerning the individual's family
members, determining their familial relationship to the proband,
and recording their state of health or cause of death. This
information is typically portrayed in the form of a family tree.
Methods for recording an individual's medical history and family
history are known in the art and may comprise printed materials
with worksheets or may comprise electronic medium in the form of
computer programs such as GeneTree of Cyrillic. In the preferred
embodiment, the collection element is integrated with other
elements of the instrument. For example, the collection element may
be integrated with the information element such that the individual
is provided with information about the genetics of different
diseases, disorders, or clinical outcomes that would be useful in a
personal or family history. The collection element may be
integrated with the instruction element such that the practitioner
can instruct the individual in the use of the element and use the
data to perform a quantitative assessment of genetic risk. In a
specific embodiment, the collection element is validated.
In a further embodiment the collection element may be linked to the
recording element to enable follow-up of the proband and family
members with information regarding the genetic test or test results
that may be relevant to clinical outcomes of the proband or family
members. For example, the collection element may incorporate email,
telephone, or mailing addresses of family members or provide the
proband with materials that can be mailed to these individuals.
Information from these family members may be incorporated in the
collection element to provide a more complete and accurate
collection of the proband's medical and family history. In a
specific embodiment, the collection element is integrated with the
certification element to assure proper authorization of procedures
to contact family members. In a specific environment, the
collection element may be integrated with the certification element
and recording element, enabling the proband and family members to
authorize the distribution of genetic and medical information,
receive-follow-up, and release genetic information to their
respective medical records
The assessment element comprises a series of questions in the form
of text and illustrative materials that are posed to the individual
to assess their retention and comprehension of information. The
legal principle underlying informed consent for genetic testing is
that an individual must have sufficient comprehension of
information to make an informed choice. The assessment element is
designed to determine whether the individual has retained and
comprehends sufficient information concerning the genetic test to
provide such a valid informed consent. The assessment element
includes text comprising basic questions covering information
presented in the information element and instruction element
concerning a genetic test for one gene, more than one gene, related
genes, a clinical outcome or a gene screen to be performed,
possible test results, DNA banking, the medical significance of
potential test results, standard of care recommendations concerning
such tests, the choices available based on the test results, the
specific benefits and risks of performing the tests, the procedure
for obtaining a sample and performing a test, the disposition and
potential future use of the sample as well as the test results,
guidelines for protecting the privacy and confidentiality of the
individual, and legal issues regarding liability. The text of the
assessment element may incorporate questions in the form of short
answers, multiple choice, true/false, matching, fill in the blank,
or other test formats known in the art. The assessment element is
integrated with other elements of the instrument. In a specific
embodiment, the assessment element is validated.
In a preferred embodiment, the assessment element comprises printed
material in the form of a questionnaire that can be completed by
the individual. In an alternative embodiment, the assessment
element is in the form of interactive electronic medium in which
the individual reads and responds to questions on a computer or the
Internet. In another alternative embodiment, the assessment element
is integrated with the instruction element and the practitioner
reads the questions to the individual and the individual either
provides answers on a worksheet or responds orally and the
practitioner records the answers. In a specific embodiment, the
assessment element is integrated with the information element with
provides the individual with sufficient information to correctly
answer questions in the assessment, is integrated with the
instruction element which provides the practitioner with directions
on administering the assessment and scoring the results, is
integrated with the certification element such that certification
can only be provided if the individual exhibits a minimum number of
correct answers on the assessment, and integrated with the
recording element which incorporates the individual's responses to
the questions and/or the score on the assessment.
The labeling element comprises materials that are to be attached to
a sample or a sample collection device to identify the individual,
direct the sample to the appropriate laboratory, and designate how
the sample is extracted and banked, and what test is performed. The
labeling element may also designate, either in text, color code, or
other recognized medium, whether the sample is to be preserved,
whether DNA is to be banked, and what uses may be made of the
sample. In preferred embodiments, the element comprises one or more
than one copy of printed materials that form a label that is
affixed to the sample or one or more sample collection devices used
in the course of obtaining a sample, handling the sample, banking
DNA, and performing the genetic test. In a specific embodiment, the
labeling element comprises printed materials with an adhesive
backing that can be separated from the instrument and attached
directly to the sample. In alternative embodiments, the labeling
element comprises an electronic medium for generating information
required for the label and a method for printing the label that can
be attached to the sample. In preferred embodiments, the labeling
element is integrated with other elements of the instrument. In a
specific embodiment, the labeling element is validated.
In a specific embodiment of this invention, the instruction element
includes text and/or illustrative materials directing the
practitioner how to use the labeling element so that the sample is
properly collected, labeled, and directed to the laboratory. In a
specific embodiment, the labeling element is integrated with the
recording element so that there is a record that the sample has
been obtained, processed and sent, and the status of the sample,
test procedure, and test results can be tracked. In another
specific embodiment, the labeling element is integrated with the
certification element so that the laboratory receiving the sample
is notified that an informed consent has been obtained for the
specific test and that a prescription has been provided by the
practitioner.
In a preferred embodiment of this invention the labeling element
encodes the identity of the individual to preserve their privacy
and confidentiality. This may involve attaching a label to the
sample that has personal information encoded or in a form such as a
barcode or personal identification number that is not readily
identifiable except to those with appropriate authorization.
The billing element comprises forms required for direct payment by
the individual or forms required to obtain reimbursement or arrange
payment by a third party payor. Such elements are commonly known in
the art and may comprise forms to be completed by the individual
and/or the practitioner with a credit card number, insurance policy
number, and billing codes. Alternatively these forms may comprise
electronic medium or an interactive electronic medium designed to
print a form with information from the individual or practitioner.
In the preferred embodiment the billing element is integrated with
other elements of the instrument.
The recording element comprises materials designed to be placed in
an appropriate personal medical records maintained by the
practitioner, provided to the individual for their own records, and
deposited in other records as may be required, for example, by the
practitioner, payor, or regulations The recording element
constitutes the legal record of the informed consent process,
providing a record of the procedures used to obtaining the consent,
including, for example, information provided to the individual and
any assessment that is performed, documentation of the test that is
to be performed and any restrictions on the use of the information
or sample, and certification of the informed consent. The process
of maintaining medical records is known in the art and may involve
printed materials or electronic medium. In the preferred
embodiment, the recording element is integrated with other elements
of the instrument. In specific embodiments the recording element
may incorporate one or more of the following: a checklist
documenting the procedures for informed consent that were used by
the practitioner from the instruction element, the personal medical
history and family history of the individual from the collection
element, the informed consent and prescription from the
certification element, information used to label the sample from
the labeling element, and information for billing from the billing
element.
In preferred embodiments, one or more than one of the elements of
the instrument are designed so that information entered into one
element is also incorporated into the recording element in a form
suitable for incorporation in the medical record or provided to the
individual. In a preferred embodiment these copies comprise printed
materials and the design of the integrated instrument enables these
pages to be physically separated from their respective elements and
the complete instrument for inclusion in the record. In alternative
embodiments, the instrument is designed so that carbon copies of
essential information are imprinted on the recording element, for
example, responses or scores from the assessment instrument, the
prescription provided by the practitioner, or the checklist used by
the practitioner may be copied directly onto a recording element in
carbon copy. Informed consent must be generally completed in
several copies including one that is given to the individual and
one that becomes part of the individual's record. In a specific
embodiment the recording element incorporates a copy of the
certification element (informed consent document). In an
alternative embodiment, these copies comprise electronic medium
that can produce materials for inclusion in the record in either
printed material or electronic medium.
The recording element will commonly contain other information to
identify the individual including a medical record number,
information on the referring practitioner, information on payors,
information on the disposition of the sample, whether DNA has been
banked, restrictions on the use of the sample and banked DNA,
restrictions on the use of personal information, and directions on
how to contact the individual or their practitioner with the test
results. State and federal laws set standards for the protection of
genetic information in individual medical records. The recording
element also incorporates codes, mechanisms, procedures, and
physical barriers, or fire walls necessary to protect the privacy
of such information. For example, patient information may be
represented in bar code or personal identifying code,
de-identified, or encrypted. Methods and procedures for protecting
the privacy of individual medical records are well known to those
skilled in the art. This invention specifically provides for the
individual to provide necessary releases in the certification
element as may be required by law for the dissemination of
information entered into the recording element to practitioners or
others authorized by the individual.
The training element comprises text and illustrative materials
designed to train practitioners in the use of the instrument for
obtaining informed consent and methods for obtaining informed
consent using said instruments. Materials designed for use in
medical education and Continuing Medical Education (CME) are known
in the art and frequent comprise printed materials, electronic
medium, or mixed medium, for example, including books, CDs, web
sites, pamphlets, slides, presentations. The element may comprise
curriculum to be used in medical education or CME as well as
illustrative materials that can be used in training and education.
In a preferred embodiment, materials used to train practitioners in
the use of the instrument are integrated with the integrated with
instrument, for example, by describing the composition or methods
of using the instrument, incorporating information, text or
illustrative materials from the instrument, diagrams or
incorporating representations of the instrument itself.
The quality control element comprises a reporting form that is used
to determine whether performance specifications are being met by
the practitioner using the instrument in the field. This element
contains information about the process used to obtain informed
consent that can be used for a review of the performance of the
instrument and the practitioner. A specific utility of this
invention is the standardization and validation of procedures for
obtaining informed consent. There is also provided with this
invention a method for performing quality assessment and quality
control of the informed consent process using the quality control
element. This method involves the reporting and review of results
from the assessment element to determine whether performance
specifications are being achieved in the field by different
practitioners using the instrument in different populations and
healthcare settings. The method may involve analysis of test
results from random or selected regions or populations, instruments
dealing with specific tests, the specialty or subspecialty of the
practitioner, the language of the instrument, or the health,
language, ethnic origin, or socioeconomic status of the individual.
The results of such analysis can be used to measure the performance
of individual practitioner against performance specifications or to
further refine the integrated instrument, for example through
modifications of the instruction element or modifications of a
training element. The quality control element is integrated with
other elements of the instrument. For example, the instruction
element may inform the practitioner concerning quality control
procedures, and the quality control element may incorporate data
from the assessment element and the recording element.
The indemnification element certifies that the methods and
instruments described in this invention were used to obtain consent
and that these methods are validated and may provide
indemnification against claims related to the adequacy of the
informed consent process. The failure to obtain a proper informed
consent may render a practitioner liable to legal action on the
part of the individual or government regulatory body governing
medical practice claiming that the individual was not adequately
informed prior to certifying their consent or a test being
performed. Use of the integrated and validated instruments and
methods of this invention as described herein is designed to
achieve certain performance specifications and standards including
a minimum level of retention and understanding of information
concerning the genetic test by the individual and the effective
handling of the sample and genetic information.
The indemnification element documents the procedures that were used
by the practitioner to obtain informed consent. The indemnification
element is integrated with other elements of the instrument. For
example, the indemnification element may incorporate elements of
the information element to document the information that was
provided to the individual, may incorporate a checklist from the
instruction element to document that procedure were followed, may
incorporate the results of the assessment element to demonstrate
that a requisite level of retention and understanding was observed,
and may incorporate the certification element to establish that the
individual certified their consent. The indemnification element may
be incorporated in the recording element and maintained with the
individual's medical record, or filed with a central facility. In a
further aspect of this invention, practitioners filing an
indemnification element documenting their effective use of the
instrument may receive indemnification against claims related to
the adequacy of the informed consent process.
Some exemplary instruments are described below. These are provided
for the purpose of illustrating the invention and are not intended
to limit its scope.
Integrated Instruments Containing an Information Element
In a preferred embodiment of this invention, the instrument
contains an information element integrated with an instruction
element and a certification element, and with one or more than one
of the following, optionally integrated, elements: a collection
element, an assessment element, a labeling element, a billing
element, a recording element, a training element, a quality control
element and an indemnification element. In another embodiment, this
instrument contains an integrated information element, an
integrated instruction element and an integrated certification
element, optionally integrated with two, three, four, five, six,
seven or eight of the elements set forth above.
Integrated Instrument Containing an Assessment Element
In a preferred embodiment of this invention, the instrument
contains an instruction element integrated with an information
element and a certification element and further contains an
optionally integrated assessment element. In another embodiment,
this instrument also contains an optionally integrated collection
element. In yet another embodiment, this instrument additionally
contains one or more than one of the following, optionally
integrated elements: a labeling element, a billing element, a
recording element, a training element, a quality control element
and an indemnification element. In another embodiment, this
instrument contains an instruction element integrated with an
information element and a certification element and optionally
integrated with two, three, four, five, six, seven or eight of the
elements set forth above.
Integrated Instrument Containing a Collection Element
In a preferred embodiment of this invention, the instrument
contains an information element, instruction element and
certification element, optionally integrated with a collection
element. In another embodiment, this instrument contains in
addition one or more than one of the following integrated elements:
an assessment element, a labeling element, a billing element, a
recording element, a training element, a quality control element
and an indemnification element. In yet another embodiment, this
instrument contains an integrated information element, integrated
instruction element, integrated certification element and an
integrated collection element, optionally integrated with two,
three, four, five, six, seven or eight of the elements set forth
above.
Integrated Instrument Containing a Collection Element and an
Assessment Element
In a preferred embodiment of this invention, the instrument
contains a certification element integrated with an instruction
element, with an information element and with a collection element
and an assessment element. Additionally, this embodiment may
further include one or more than one of the following optionally
integrated elements: a labeling element, a billing element, a
recording element a training element, a quality control element and
an indemnification element. In a specific embodiment of this
invention, the instrument contains a certification element
integrated an instruction element, an information element, a
collection element and an assessment element, and optionally
integrated with two, three, four, five, six, or seven of the
elements listed above.
Training Element, Quality Control Element, and Indemnification
Elements
A preferred embodiment of this invention is an instrument for
obtaining informed consent containing an integrated training
element. In such embodiment, the training element is integrated
with the instruction element, the information element and the
certification element. In an alternative embodiment, the training
element is integrated with these three element and with an
assessment element or a collection element, or both assessment and
collection elements. In another alternative embodiment, the
training element is integrated with these three elements and with
one or more of the following optionally integrated elements:
recording element, labeling element, billing element, quality
control element, and indemnification element.
A specific object of this invention is an instrument for obtaining
informed consent containing an integrated quality control element.
In such embodiment, the quality control element is integrated with
the instruction element, the information element and the
certification element. In an alternative embodiment, the quality
control element is integrated with these three element and with an
assessment element or a collection element, or both assessment and
collection elements. In another alternative embodiment, the quality
control element is integrated with these three elements and with
one or more of the following elements: recording element, labeling
element, billing element, training element, and indemnification
element. In a preferred embodiment, the quality control element is
integrated with these three elements and with the reporting
element. In a preferred embodiment, the quality control element is
integrated with these three elements and with the training element.
In further embodiments, the quality control element is integrated
with two or more than two of the collection element, the assessment
element, the recording element, the labeling element, the billing
element, the training element and the indemnification element.
A specific object of this invention is an instrument for obtaining
informed consent integrated with an indemnification element. In
such embodiment, the indemnification element is integrated with the
information element, the instruction element and the certification
element. In an alternative embodiment, the indemnification element
is integrated with these three elements and an assessment element
or a collection element or with both of these elements. A specific
embodiment is the integration of the indemnification element with
these three elements and one or more than one of the assessment
element, the collection element, the quality control element, the
labeling element, the billing element, the recording element, and
the training element. In a preferred embodiment the indemnification
element incorporates a checklist from the instruction element. In a
preferred embodiment the indemnification element incorporates the
assessment element and the certification element.
Integrated and Validated Instrument
A preferred embodiment of this invention is a validated instrument
for obtaining informed consent comprising the following integrated
elements: (a) an information element for an individual concerning a
genetic test for one gene, more than one gene, related genes, a
clinical outcome or a gene screen; (b) an instruction element that
can be used by a practitioner in providing instruction to the
individual and guidance in the use of the instrument and obtaining
informed consent; (c) a collection element of information
concerning the individual's personal medical history or their
family medical history; (d) an assessment element of the
individual's retention or comprehension of said information; (e) a
certification element of the individual's consent for said test;
(f) a labeling element for labeling a sample or sample collection
device obtained for genetic testing with the identity of the
individual; (g) a billing element either for direct payment by the
individual or through a reimbursement agency; and (h) a recording
element that can be attached to the individual's medical
record.
A specific embodiment of this invention is a validated instrument
for obtaining informed consent that contains two or more of the
following, optionally integrated, elements, an information element,
an instruction element, a collection element, an assessment
element, a certification element, a labeling element, a billing
element, a recording element, a training element, a quality control
element, and a indemnification element. In such embodiments, the
instrument contains two, three, four, five, six, seven, eight,
nine, or ten of these elements. Another specific embodiment of this
invention is a validated instrument for obtaining informed consent
that contains an instruction element integrated with one or more
than one of the following elements: an information element, a
collection element, an assessment element, a certification element,
a labeling element, billing element, a recording element, a
training element, a quality control element, and a indemnification
element. In specific embodiment of this invention, the instrument
contains a instruction element integrated with two, three, four,
five, six, seven, eight or nine of said elements.
Integrated Instruments Useful in the Field of Medicine
A preferred embodiment of this invention is an instrument for
obtaining consent for a genetic test for predicting a clinical
outcome or determining the genetic risk of a clinical outcome,
which instrument comprises the following integrated elements: (a)
an information element for an individual concerning a genetic test
for one gene, more than one gene, related genes, associated with a
clinical outcome; (b) an instruction element that can be used by a
practitioner in providing instruction to the individual and
guidance in the use of the instrument and obtaining informed
consent; (c) a collection element of information concerning the
individual's personal medical history or their family medical
history; (d) an assessment element of the individuals retention or
comprehension of said information; (e) a certification element of
the individual's consent for said test; (f) a labeling element for
labeling a sample or sample collection device obtained for genetic
testing with the identity of the individual; (g) a billing element
either for direct payment by the individual or through a
reimbursement agency; and (h) a recording element that can be
attached to the individual's medical record.
A specific embodiment of this invention is an instrument for
obtaining consent for a genetic test for predicting a clinical
outcome or determining the genetic risk of a clinical outcome that
contains an instruction element integrated with an information
element and with a certification element, and optionally integrated
with one or more than one of the following elements: a collection
element, an assessment element, a labeling element, a billing
element, a recording element, a training element, a quality control
element, and an indemnification element. In specific embodiment of
this invention, the instrument contains the integrated instruction,
information and certification elements optionally integrated with
two, three, four, five, six, seven, or eight of the other of the
elements listed above.
C. Method of Use
There is provided by this invention a novel method for obtaining
informed consent in which the practitioner uses an integrated
instrument for obtaining such consent, more specifically a
validated instrument. In specific embodiments, the method involves
the use of an instrument with the following integrated elements: an
information element, an instruction element, and a certification
element, and optionally one or more elements selected from the
group consisting of a collection element, an assessment element, a
labeling element, a billing element, a recording element, a
training element, a quality control element and an indemnification
element. The method comprises completing a checklist of steps to
obtain an informed consent using the instrument and the
practitioner indicates on the checklist the steps that have been
performed and completed. In a preferred embodiment, the method
involves the steps of: (a) procuring an integrated instrument for
obtaining informed consent to a genetic test from an individual,
which instrument contains an information element, an instruction
element and a certification element; (b) conveying to the
individual information concerning the genetic test using the
integrated information element; (c) instructing an individual
according to the directions contained in the integrated instruction
element; and (d) certifying the individual's consent for the test
using the integrated certification element.
In addition, the method may include collecting a personal medical
history and family history using an integrated collection element
and may further or additionally include assessing the individual's
retention or comprehension of the information using an integrated
assessment element. Optionally, the method may further include the
steps of labeling a sample with the identity of the individual
using an integrated labeling element, and recording information
concerning the informed consent process using an to integrated
recording element.
In a preferred embodiment, the method further includes posting of
one or more elements of an integrated instrument for obtaining
informed consent. Posting makes the element or elements available
as a resource to practitioners in printed or electronic medium (for
example, on an Internet site or computer) or by incorporation of
the element in policies, practices, guidelines, recommendations,
training materials, or lessons. The posting of more than one
element may be by the same or different means. For example, an
instruction element may be posted in a procedure manual, and
information elements provided as booklets to the individual, and
recording elements provided as part of a medical record system. For
example, an instruction element from an integrated instrument for
obtaining informed consent may be posted with or without any of the
additional elements included in the instruments and methods of the
invention.
In detail, the step of "procuring" refers to obtaining an
integrated instrument useful for obtaining informed consent for a
specific gene, more than one related gene, a clinical outcome, or a
gene screen. For example, an instrument may be procured by
purchasing the instrument in written or electronic form,
downloading the instrument from an Internet site, accessing the
instrument on a computer, or printing it from a computer. Elements
of the integrated instrument may be procured separately. For
example, selected elements may be procured in written form, and
others downloaded from an Internet site. Procuring also refers to
the retrieval of elements that have been posted. Alternatively, one
or more elements may be posted after they are procured by other
means. Procuring may involve a payment for the instrument or one or
more elements of the instrument or may be free of charge.
The step of "posting" of an element means to make it generally
available to individuals or practitioners, for example by placing
it on a web site, providing it as a resource in printed or
electronic medium accessible to individuals or practitioners.
Alternatively, posting may refer to policies, business practices,
guidelines, recommendations, training materials, lessons that
incorporate the use of one or more of said element.
The step of "conveying" refers to the delivery of an information
element to an individual designed to give the individual with
background information on a genetic test sufficient to provide an
informed consent. For example, the individual can be given a
booklet containing information about the genetic test or provided
with access to an Internet site or computer with this information.
Preferably conveying is performed using an information element
integrated with one or more elements of the instrument.
The step of "instructing" refers to giving of instruction to an
individual by a practitioner concerning a genetic test. Preferably,
instructing is performed by the practitioner according to
directions included in an instruction element integrated with one
or more elements of the instrument.
The step of "collecting" refers to obtaining a personal medical
history and family history from an individual. Preferably,
collecting is performed using a worksheet and instructions included
in a collection element integrated with one or more elements of the
instrument.
The step of "assessing" refers to an assessment of an individual's
retention or comprehension of information sufficient to provide an
informed consent by presenting the individual with questions
concerning aspects of the test and testing process and scoring
their responses. Preferably assessing is performed using an
assessment element integrated with one or more elements of the
instrument element integrated with one or more elements of the
instrument.
The step of "certifying" refers to the completion of a legal
informed consent document by an individual and appropriate
witnesses. Preferably certifying is performed using a certification
element integrated with one or more elements of the instrument.
The step of "labeling" refers to the labeling of a sample with
information required for the proper handling of the sample,
performance of the test, and protection of individual privacy.
Preferably, labeling is performed using a labeling element
integrated with one or more elements of the instrument.
The step of "recording" refers to the placement of essential
information concerning the informed consent process and the
individual's medical and family history in a medical record.
Preferably recording is performed using a recording element
integrated with one or more elements of the instrument.
Indemnifying refers to the issuance of an insurance policy which
pays for claims against the practitioner related to the quality of
the informed consent obtained using the instrument.
Sample Collection and Diagnostic Devices
An additional embodiment of this invention is kit comprising a
sample collection device and an integrated instrument for obtaining
informed consent for a genetic test. Sample collection devices are
known in the art. Samples can be collected using routine procedures
from blood drawing and tubes that enable the separation of white
blood cells (that contain DNA) from red blood cells, serum, or
plasma. Specialized devices are also known in the art and approved
by the FDA for sample collection. The OraSure Oral Specimen
Collection Device from Orasure Technologies, Inc. is one example of
an FDA-approved sample collection device that can be used for the
collection of DNA from the oral mucosa for clinical applications.
Another example is S&S 903 Specimen Collection Paper from
Schleicher & Schuell, GmbH is another FDA listed device that is
widely used for adult sample collection, including genetic studies.
S&S 903 Specimen Collection Paper, is used widely for newborn
screening and has also been used for genetic studies. S&S 903
Specimen Collection Paper has also been incorporated into single
and multi-part forms and forms and customized printing is available
from the manufacturer with biologically inactive inks and glues
that enable the paper to incorporate information or codes for
patient identification, processing, and lot traceability. The 903
device can be used to collect blood or body fluids such as urine,
tears, or saliva that are spotted and dried onto the 903 paper. In
this form the sample is stable and can be mailed to centralized
labs for analysis, sample extraction, or DNA banking.
An additional embodiment of this invention is kit comprising a
sample collection device and an integrated instrument for obtaining
informed consent for a genetic test. In one example, the sample
collection device is printed S&S 903 paper that is included as
part of the labeling element of the integrated instrument.
Alternatively, the sample collection device may be included in the
recording element and may be comprised of a multi-part form
comprising S&S 903 paper for sample collection. In a preferred
example, a booklet comprising one or more of the elements of the
integrated element may contain a page made of S&S 903 paper
which is perforated or glued to the booklet for easy separation.
The booklet may be constructed such that information concerning the
individual's identity, the test to be performed, handling of the
sample and test results, and valid certification of consent for DNA
banking and testing is entered simultaneously onto a sample
collection device such as S&S903 paper and onto other elements
of the instrument, for example, by constructing the instrument such
that carbon copies are made on one or more elements such as the
checklist within the instruction element, the labeling element, or
certification element. In another preferred example, sample
collection device, for example, S&S 903 paper, may be
integrated with other elements of the instrument, by describing the
process for sample collection in the information element or
directions for obtaining and processing a sample in the instruction
element. It will be recognized by those skilled in the art that
other sample collection devices may be integrated with the
instrument for informed consent in an analogous manner.
EXAMPLE 1
Examples of Genetic Tests
A. Genetic Tests Predicting the Risk of Common Disease.
Most common diseases are considered to be multifactorial or
polygenic, meaning that many different genes may contribute to the
risk of the disorder. Examples include:
TABLE-US-00001 Disorder Genetic test Cancer Breast Cancer (BRCA1
)*; BRCA1; Ovarian Cancer (BRCA1) Breast Cancer (BRCA2)*; BRCA2;
Ovarian Cancer (BRCA2) p53, p21, p16 Ataxia Telangectasia NHPCCm
FAP (colon cancer) Medullary Thyroid Carcinoma; MTC Alzheimer's
Disease Apolipoprotein E amyloid precursor protein presenilin-1,
presenilin-2 2-macroglobulin alpha 1-antichymotrypsin Heart attack,
Apolipoprotein E stroke Lipoprotein lipase LDL receptor MTHFR
Angiotensinogen ALS Superoxide Dismutase (SOD) COPD alpha
1-antitrypsin (AAT) Anemia hemoglobin S hemoglobin C thalassemia
(alpha) thalassemia (beta) G-6 PD Liver failure Hemochromatosis
Spina Bifida MTHFR Arthritis HLA-B, HLA-D Periodontal IL-1 disease
Osteoporosis col1A1
B. Genetic Tests Predictive of Drug Response.
Variations in genes that affect the metabolism of drugs can
increase drug levels, drug toxicity and drug interactions. Genetic
tests can be used to avoid drugs that have a higher probability of
toxicity and individualize the dose to maximize the therapeutic
benefit while minimizing toxicity. Examples include:
TABLE-US-00002 Gene test Drugs and chemical affected CYP1A1
Chlorinated benzenes (environmental toxin) CYP1A2 Caffeine,
phenacetin, warfarin, Erythromycin, Ropivacaine, Haloperidol,
antipyrine, theophylline, Paracetamol CYP2C8 TCA, Diazepam,
Hexabarbitone CYP2C9/10 Phenytoin, S-warfarin, Diclofenac,
Tolbutamide CYP2C19 Mephenytoin, Diazepam (Valium), TCA CYP2D6
Debrisoquine, Codeine, Dextrometorphan, b-blockers, SSRIs, others
CYP2E1 Paracetamol, Isoflurane, Sevoflurane, Methoxyflurane,
Enflurane, CYP3A4 Nifedipine, Dextrometorphan, Alfentanil,
Sufentanil, Fentanyl, Erythromycin, Lignocaine, Ropivacaine,
Midazolam, Codeine, Granisetron, Hydrocortisone CYP3A5 Caffeine,
Diltiazem CYP3A7 Midazolam CYP17 Pregnolone CYP19 Testosterone
CYP21A2 17-hydroxyprogesterone
C. Variations in Genes that Affect Drug Targets and Drug Response
May Affect the Safety and Efficacy of a Drug.
Genetic tests can be used to avoid drugs that have a higher
probability of toxicity and individualize the dose to maximize the
therapeutic benefit while minimizing toxicity. Examples
include:
TABLE-US-00003 Gene test Drugs or chemicals affected Factor V Oral
contraceptives Prothrombin Oral contraceptives TPMT (thiopurine
methyltransferase) Azothioprine, mercaptopurine (purine analogues)
5' lipoxegenase Zilutin (5' lipoxegenase inhibitors) CETP
(cholesterol ester transfer Pravastatin, others (statins) protein)
ApoE (apolipoprotein E) Tacrine (cholinesterase inhibitors,
muscarinic agonists, others) G-6 PD sulfur drugs
Pseudocholinesterase pseudocholinesterase inhibitors Beta-receptor
Isoproterenol (beta-agonists) Serotonin transporter SSRI
antidepressants (Prozac, Pindolol, others) Acetyltransferase
isoniazid, others ADH(2h) (aldehyde dehydrogenase) alcohol ACE
(angiotensin converting enzyme Enalpril, others Opioid receptors
Endorphins, morphine
Genetic Tests for Inherited or Genetic Disorders.
A large number or inherited genetic diseases are caused by
well-characterized mutations in genes that impair the function of a
gene or cause a gene to have dominant, adverse effects. The
following is partial list of genetic tests for diseases that are
generally considered to be genetic or congenital.
DiGeorge Syndrome 2
Velocardiofacial Syndrome 2 1p36 Deletion Syndrome 22q11 Deletion
Syndrome
Cayler Cardiofacial Syndrome Conotruncal Anomaly Face Syndrome
DiGeorge Syndrome Opitz G/BBB Sedlackova Syndrome Shprintzen
Syndrome Velocardiofacial Syndrome 3-Methylglutaconic Aciduria
46,XY Gonadal Dysgenesis Achalasia-Addisonianism-Alacrima Syndrome
Achondrogenesis Achondrogenesis Type IA Achondrogenesis Type IB
Achondrogenesis Type II Achondroplasia Acute Hepatic Porphyria
Acute Intermittent Porphyria Adenosine Monophosphate Deaminase 1
Adrenoleukodystrophy, X-Linked Adrenomyeloneuropathy Alagille
Syndrome Albinism Ocular Albinism, X-Linked Oculocutaneous Albinism
Oculocutaneous Albinism Type 1 Oculocutaneous Albinism Type 1A
Oculocutaneous Albinism Type 1B Oculocutaneous Albinism Type 2 (P
Related) Oculocutaneous Albinism Type 3 (TRP1 Related)
Aldosteronism, Sensitive to Dexamethasone Alpha-1-Antitrypsin
Deficiency Alpha-Mannosidosis Alpha-Thalassemia Alpha-Thalassemia
X-Linked Mental Retardation Syndrome Alport Syndrome Alport
Syndrome, Autosomal Dominant Alport Syndrome, Autosomal Recessive
Alport Syndrome, X-Linked Alzheimer Disease Early Onset Familial
Alzheimer Disease Alzheimer Disease Type 1 Alzheimer Disease Type 3
Alzheimer Disease Type 4 Late-Onset Familial Alzheimer Disease
Alzheimer Disease Type 2 Alzheimer Disease Type 5 Amino Adipic
Aciduria Amyotrophic Lateral Sclerosis Androgen Insensitivity
Syndrome Complete Androgen Insensitivity Syndrome Mild Androgen
Insensitivity Syndrome Partial Androgen Insensitivity Syndrome
Angelman Syndrome Anhaptoglobinemia Aniridia
Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Ankylosing
Spondylitis Apolipoprotein E Genotyping Apparent Mineralocorticoid
Excess Syndrome Argininemia Argininosuccinicaciduria Aromatic
L-Amino Acid Decarboxylase Deficiency Aspartylglycosaminuria
Atelosteogenesis Type II Autoimmune Polyendocrinopathy Syndrome
Type 1 Autosomal Recessive Adrenoleu kodystrophy Autosomal
Recessive Congenital lchthyosis Congenital lchthyosiform
Erythroderma Non-Bullous Congenital lchthyosiform Erythroderma
Avellino Corneal Dystrophy Barth Syndrome Beckwith-Wiedemann
Syndrome Beta-Mannosidosis Beta-Methylcrotonylglycinuria
Beta-Thalassemia Thalassemia Intermedia Thalassemia Major
Thalassemia Minor Biotin-Responsive Multiple Carboxylase
Deficiencies Biotinidase Deficiency Holocarboxylase Synthetase
Deficiency Bloom Syndrome Breast Cancer Genetics BRCA1 and BRCA2
Hereditary Breast/Ovarian Cancer BRCA1 Hereditary Breast/Ovarian
Cancer BRCA2 Hereditary Breast/Ovarian Cancer Brugada Syndrome
CADASIL Camurati-Engelmann Disease Canavan Disease
Carbamoylphosphate Synthetase I Deficiency Carney Complex Carnitine
Deficiency, Systemic Carnitine Palmitoyltransferase IA (liver)
Deficiency Carnitine Palmitoyltransferase II Deficiency
Carnitine-Acylcarnitine Translocase Deficiency Cartilage-Hair
Hypoplasia Catecholaminergic Ventricular Tachycardia
Catecholaminergic Ventricular Tachycardia, Dominant
Catecholaminergic Ventricular Tachycardia, Recessive Celiac Disease
Cerebrotendinous Xanthomatosis Charcot-Marie-Tooth Disease, Type 4B
Charcot-Marie-Tooth Hereditary Neuropathy Charcot-Marie-Tooth
Neuropathy Type 1 Charcot-Marie-Tooth Neuropathy Type 1A
Charcot-Marie-Tooth Neuropathy Type 1B Dejerine-Sottas Disease
Charcot-Marie-Tooth Neuropathy Type 1C Charcot-Marie-Tooth
Neuropathy Type 1D Charcot-Marie-Tooth Neuropathy Type 2
Charcot-Marie-Tooth Disease, Neuronal/Axonal Charcot-Marie-Tooth
Neuropathy Type 2A Charcot-Marie-Tooth Neuropathy Type 2B
Charcot-Marie-Tooth Neuropathy Type 2C Charcot-Marie-Tooth
Neuropathy Type 2D Charcot-Marie-Tooth Neuropathy Type 2E
Charcot-Marie-Tooth Neuropathy Type 4 Charcot-Marie-Tooth
Neuropathy Type 4A Charcot-Marie-Tooth Neuropathy Type 4B
Charcot-Marie-Tooth Neuropathy Type 4C Charcot-Marie-Tooth
Neuropathy Type 4D Charcot-Marie-Tooth Neuropathy Type 4E
Charcot-Marie-Tooth Neuropathy Type 4F Dejerine-Sottas Disease
Charcot-Marie-Tooth Neuropathy Type X Hereditary Neuropathy with
Liability to Pressure Palsies CHILD Syndrome Chondrodysplasia
Punctata, X-Linked Dominant Choroideremia Citrullinemia Clinical
Confirmation of Mutations Identified in Research Labs Cockayne
Syndrome Cockayne Syndrome Type A Cockayne Syndrome Type B Cockayne
Syndrome Type I Cockayne Syndrome Type II Cockayne Syndrome Type
III Xeroderma Pigmentosa-Cockayne Syndrome Coffin-Lowry Syndrome
Congenital Adrenal Hyperplasia 11 beta Hydroxylase Deficiency 17
alpha Hydroxylase Deficiency 21-Hydroxylase Deficiency 3 beta
Hydroxysteriod Dehydrogenase Deficiency Cholesterol Desmolase
Deficiency Congenital Contractural Arachnodactyly Congenital
Disorders of Glycosylation Congenital Erythropoietic Porphyria
Congenital Hypomyelination Congenital Insensitivity to Pain with
Anhidrosis Congenital Muscular Dystrophy Congenital Muscular
Dystrophy with Cerebellar Hypoplasia Congenital Muscular Dystrophy
with Early Spine Rigidity Congenital Muscular Dystrophy with
Integrin alpha 7 Mutations Congenital Muscular Dystrophy with
Merosin Deficiency Congenital Muscular Dystrophy with Mitochondrial
Structural Abnormalities Congenital Muscular Dystrophy,
Merosin-Positive Fukuyama Muscular Dystrophy Muscle-Eye-Brain
Disease Walker-Warburg Syndrome Coronal Synostosis Coronary Artery
Disease Risk Factor (ACE) Coronary Artery Disease Risk Factor
(PLA1/2) Craniosynostosis FGFR-Related Craniosynostosis Syndromes
FGFR1-Related Craniosynostosis SyndromePfeifferSyndrome Type 1, 2,
and 3 FGFR2-Related Craniosynostosis Syndromes Apert Syndrome
Beare-Stevenson Syndrome Crouzon Syndrome Jackson-Weiss Syndrome
Pfeiffer Syndrome Type 1, 2, and 3 FGFR3-Related Craniosynostosis
Syndromes Crouzon Syndrome with Acanthosis Nigricans Muenke
Syndrome Cri du Chat Syndrome Cystic Fibrosis Congenital Bilateral
Absence of the Vas Deferens Cystinosis Intermediate Cystinosis
Nephropathic Cystinosis Non-Nephropathic Cystinosis Cystinuria
Cytochrome C Oxidase Deficiency Darier Disease Diabetes Mellitus,
Noninsulin-Dependent Diabetes Mellitus, Transient Neonatal
Diastrophic Dysplasia Disorders of Galactose Metabolism
Galactokinase Deficiency Galactose Epimerase Deficiency
Galactosemia Variant Galactosemias Duarte VariGalactosemia
Disorders of Phenylalanine Metabolism Phenylalanine Hydroxylase
Deficiency Non-PKU Hyperphenylalanemia Phenylketonuria Variant PKU
Tetrahydrobiopterin deficiencies 6-Pyruvoyl-Tetrahydropterin
Synthase Deficiency Dihydropteridine Reductase Deficiency (DHPR)
GTP Cyclohydrolase-1 Deficiency (GTPCH) Pterin-4a Carbinolamine
Dehydratase Deficiency Tetrahydrobiopterin deficiencies GTP
Cyclohydrolase 1-Deficient DRD Sepiapterin Reductase Deficiency
(SR) Dopa-Responsive Dystonia GTP Cyclohydrolase 1-Deficient DRD
Tyrosine Hydroxylase-Deficient DRD Down Syndrome Critical Region
Dubin-Johnson Syndrome Dystrophinopathies Duchenne/Becker Muscular
Dystrophy Becker Muscular Dystrophy Duchenne Muscular Dystrophy
X-Linked Dilated Cardiomyopathy Early-Onset Primary Dystonia
Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome
Ehlers-Danlos Syndrome, Arthrochalasia Type Ehlers-Danlos Syndrome,
Kyphoscoliotic Form Ehlers-Danlos Syndrome, Vascular Type
Emery-Dreifuss Muscular Dystrophy Epidermolysis Bullosa
Dystrophica, Bart Type Epidermolysis Bullosa Dystrophica,
Cockayne-Touraine Type Epidermolysis Bullosa Dystrophica,
Hallopeau-Siemens Type Epidermolysis Bullosa Dystrophica, Inversa
Type Epidermolysis Bullosa Dystrophica, Pasini Type Epidermolysis
Bullosa Junctional, Disentis Type Epidermolysis Bullosa Junctional,
Herlitz-Pearson Type Epidermolysis Bullosa Letalis with Pyloric
Atresia Epidermolysis Bullosa Simplex Epidermolysis Bullosa Simplex
with Mottled Pigmentation Epidermolysis Bullosa Simplex,
Dowling-Meara Type Epidermolysis Bullosa Simplex, Koebner Type
Epidermolysis Bullosa Simplex, Recessive Epidermolysis Bullosa
Simplex, Weber-Cockayne Type Epidermolysis Bullosa with Muscular
Dystrophy Epidermolysis Bullosa, Pretibial Epidermolytic
Hyperkeratosis Epidermolytic Palmoplantar Keratoderma
Erythrokeratodermia Variabilis Erythropoietic Protoporphyria
Ethylmalonic Encephalopathy Fabry Disease Cardiac Variant Fabry
Disease Classic Fabry Disease Facioscapulohumeral Muscular
Dystrophy Familial Atypical Mycobacteriosis Familial Colon Cancer
Syndromes Colon Cancer (APC 11307K related) Familial Adenomatous
Polyposis Attenuated FAP Gardner Syndrome Turcot Syndrome
Hereditary Non-Polyposis Colon Cancer Turcot Syndrome Juvenile
Polyposis Syndrome PTEN Hamartoma Tumor Syndrome (PHTS)
Bannayan-Riley-Ruvalcaba Syndrome Cowden Syndrome Proteus Syndrome
Proteus-Like Syndrome Peutz-Jeghers Syndrome Familial Combined
Hyperlipidemia Familial Dysautonomia Familial Hemiplegic Migraine
Familial Hemiplegic Migraine 1 Familial Hemiplegic Migraine 2
Familial Hibernia Fever Familial Lipoprotein Lipase Deficiency
Familial Malignant Melanoma Familial Mediterranean Fever Fanconi
Anemia Farber Disease Fatty Acid Oxidation Disorder, Unspecified
Fragile X Syndrome FRAXE Syndrome Frontotemporal Dementia
Amyotrophic Lateral Sclerosis/Frontotemporal Dementia
Frontotemporal Dementia with Parkinsonism-17
Disinhibition-Dementia-Parkinsonism-Amyotrophy Familial Pick's
Disease Wilhelmsen-Lynch Disease Progressive Supranuclear Palsy
Fructose 1,6 Bisphosphatase Deficiency Fucosidosis Fumarate
Hydratase Deficiency Gaucher Disease Gaucher Disease Type 1 Gaucher
Disease Type 2 (Acute) Gaucher Disease Type 3 (Subacute/Chronic)
Gaucher Disease, Cardiovascular Form Gaucher Disease,
Perinatal-Lethal Form Genotypic Gender Assignment Gilbert Syndrome
Gliosis, Familial Progressive Subcortical Glutaricacidemia Type 2
Glycerol Kinase Deficiency Glycogen Storage Disease Type Ia
Glycogen Storage Disease Type Ib Glycogen Storage Disease Type II
Glycogen Storage Disease Type III Glycogen Storage Disease Type IV
Glycogen Storage Disease Type IX Glycogen Storage Disease Type V
Glycogen Storage Disease Type VI Glycogen Storage Disease Type VII
Glycoprotein 1a Deficiency GM1 Gangliosidosis GM2 Gangliosidoses
(Hexosaminidase A- and B-Deficient) Sandhoff Disease Granular
Corneal Dystrophy Greig Cephalopolysyndactyly Syndrome
Guanidinoacetate Methyltransferase Deficiency Hailey-Hailey Disease
Hallervorden-Spatz Syndrome Hartnup Disease Hemoglobin C Hemoglobin
Constant Spring Hemoglobin D Hemoglobin E Hemoglobin O Hemoglobin S
Hemophilia A Hemophilia B Hereditary Angioneurotic Edema Hereditary
Ataxias Autosomal Dominant Hereditary Ataxias DRPLA Episodic Ataxia
Type 1 Episodic Ataxia Type 2 Spinocerebellar Ataxia Type 1
Spinocerebellar Ataxia Type 2 Spinocerebellar Ataxia Type 3
Spinocerebellar Ataxia Type 4 Spinocerebellar Ataxia Type 5
Spinocerebellar Ataxia Type 6 Spinocerebellar Ataxia Type 7
Spinocerebellar Ataxia Type 8 Spinocerebellar Ataxia Type 10
Spinocerebellar Ataxia Type12 Autosomal Recessive Hereditary
Ataxias Ataxia with Oculomotor Apraxia Ataxia with Oculomotor
Apraxia 1 Ataxia with Oculomotor Apraxia 2 Ataxia with Vitamin E
Deficiency (AVED) Ataxia-Telangiectasia Autosomal Recessive Spastic
Ataxia of Charlevoix-Saguenay Friedreich Ataxia FRDA1 FRDA2
Infantile Onset Spinocerebellar Ataxia (IOSCA) Marinesco-Sjogren
Syndrome Mitochondrial Disorders with Ataxia MERF NARP X-Linked
Recessive Hereditary Ataxias Sideroblastic Anemia and Ataxia
Hereditary Coproporphyria Hereditary Diffuse Gastric Cancer
Hereditary Fructose Intolerance Hereditary Hearing Loss and
Deafness Nonsyndromic Hearing Loss and Deafness Nonsyndromic
Hearing Loss and DeafnessAminoglycoside-Induced Deafness
Nonsyndromic Hearing Loss and Deafness, Autosomal Dominant DFNA 3
(Connexin 26) Nonsyndromic Hearing Loss and Deafness, Autosomal
Recessive DFNB 1 (Connexin 26) Nonsyndromic Hearing Loss and
Deafness, X-Linked Syndromic Hearing Loss and Deafness
Mitochondrial Disorders Diabetes and Hearing Loss Kearns-Sayre
Syndrome MELAS MERRF NARP Syndromic Hearing Loss and Deafness,
Dominant Alport Syndrome, Autosomal Dominant Branchiootorenal
Syndrome Neurofibromatosis 2 Stickler Syndrome Stickler Syndrome
Type I Stickler Syndrome Type II Stickler Syndrome Type III
Waardenburg Syndrome Waardenburg Syndrome Type II Waardenburg
Syndrome Type III Waardenburg Syndrome Type IV Syndromic Hearing
Loss and Deafness, Recessive Alport Syndrome, Autosomal Recessive
Jervell and Lange-Nielsen Syndrome LQT 1 LQT 5 Pendred Syndrome
Refsum Disease Refsum Disease, Adult Refsum Disease, Infantile
Usher Syndrome Usher Syndrome Type 1 Usher Syndrome Type 2 Usher
Syndrome Type 3 Syndromic Hearing Loss and Deafness, X-Linked
Alport Syndrome, X-Linked DFN 1 Norrie Disease X-Linked Familial
Exudative Vitreoretinopathy Hereditary Hemochromatosis Hereditary
Hemorrhagic Telangiectasia Hereditary Hemorrhagic Telangiectasia
Type 1 Hereditary Hemorrhagic Telangiectasia Type 2 Hereditary
Inclusion Body Myopathy 2 Hereditary Multiple Exostoses Multiple
Exostoses Type I Multiple Exostoses Type II Hereditary Pancreatitis
Hereditary Sensory and Autonomic Neuropathy 11 Hereditary Sensory
Neuropathy Type I Hereditary Spastic Paraplegia Hereditary Spastic
Paraplegia, Dominant Hereditary Spastic Paraplegia, Complicated SPG
9 Hereditary Spastic Paraplegia, Uncomplicated SPG 3 SPG 4 SPG 6
SPG 8 SPG10 SPG12 SPG13 Hereditary Spastic Paraplegia, Recessive
Hereditary Spastic Paraplegia, Complicated SPG 7 Hereditary Spastic
Paraplegia, Uncomplicated SPG 5 SPG 11 Hereditary Spastic
Paraplegia, X-Linked Pelizaeus-MerzbacherDisease/Spastic Paraplegia
Spastic Paraplegia 1 Hermansky-Pudlak Syndrome HPS1 HPS2 HPS3
Hexosaminidase A Deficiency Chronic and Adult-Onset Hexosaminidase
A Deficiency Juvenile (Subacute) Hexosaminidase A Deficiency
Tay-Sachs Disease Hidrotic Ectodermal Dysplasia 2 Holoprosencephaly
Nonsyndromic Holoprosencephaly, Autosomal Dominant
Holoprosencephaly 2 Holoprosencephaly 3 Holoprosencephaly 4
Holoprosencephaly 5 Syndromic Holoprosencephaly, Autosomal Dominant
Ectrodactyly and hypertelorism Martin Syndrome Pallister-Hall
Syndrome Rubinstein-Taybi Syndrome Steinfeld syndrome Syndromic
Holoprosencephaly, Autosomal Recessive Facial clefts and brachial
amelia Genoa Syndrome Hydrolethalus Syndrome Lambotte Syndrome
Meckel-Gruber Syndrome Smith-Lemli-Opitz Syndrome Homocystinuria
Huntington Disease Hydrocephalus, X-Linked Hyper IgD Syndrome
Hyperbilirubinemia, Rotor Type Hyperekplexia Hyperlipoproteinemia
Type III Hyperlysinemia Hyperoxaluria, Primary, Type I
Hyperpipecolatemia Hypochondroplasia Hypohidrotic Ectodermal
Dysplasia, Dominant Hypohidrotic Ectodermal Dysplasia, Recessive
Hypohidrotic Ectodermal Dysplasia, X-Linked Hypophosphatasia
Hypophosphatemic Rickets, Dominant Hypophosphatemic Rickets,
X-Linked Ichthyosis Bullosa of Siemens Ichthyosis, X-Linked
Identity Testing Parentage Testing Family Relatedness Maternity
Testing Paternity Testing Zygosity Testing Incontinentia Pigmenti
Kallmann Syndrome, X-Linked Krabbe Disease Lactate Dehydrogenase
Deficiency Langer Mesomelic Dwarfism Langer-Giedion Syndrome
Lattice Corneal Dystrophy Type I Lecithin Cholesterol
Acyltransferase Deficiency Leprechaunism Leri-Weill
Dyschondrosteosis Lesch-Nyhan Syndrome Li-Fraumeni Syndrome
Limb-Girdle Muscular Dystrophy Limb-Girdle Muscular Dystrophies,
Autosomal Dominant Bethlem Myopathy Caveolinopathy LGMD1A LGMD1B
Limb-Girdle Muscular Dystrophies, Autosomal Recessive Calpainopathy
Dysferlinopathy Sarcoglycanopathies Alpha-Sarcoglycanopathy
Beta-Sarcoglycanopathy Delta-Sarcoglycanopathy
Gamma-Sarcoglycanopathy Telethoninopathy Limb-Mammary Syndrome
Lissencephaly Classic Lissencephaly and Subcortical Band
Heterotopia (Agyria-Pachygyria-Band Spectrum) Baraitser-Winter
Syndrome Isolated Lissencephaly/Subcortical Heterotopia X-Linked
Lissencephaly/Subcortical Heterotopia 17-Linked
Lissencephaly/Subcortical Heterotopia Miller-Dieker Syndrome
Cobblestone Dysplasia (Lissencephaly) Cobblestone Lissencephaly
Muscle-Eye-Brain Disease Walker-Warburg Syndrome Lissencephaly
Variants with Other Anomalies Microlissencephaly Microcephaly with
Simplified Gyral Pattern, Group Microlissencephaly I
Microlissencephaly II Microlissencephaly III Long Chain
3-Hydroxyacyl-CoA Dehydrogenase Deficiency Long Chain Acyl-CoA
Dehydrogenase Deficiency Long QT Syndrome Jervell and Lange-Nielsen
Syndrome LQT 1 LQT5 Long QT Syndrome, Dominant LQT 1 LQT 2 LQT 3
LQT 4 LQT 5 LQT 6 Lowe Syndrome Lymphoproliferative Disease,
X-Linked Malignant Hyperthermia Susceptibility Marfan Syndrome
Medium Chain 3-Ketothiolase Deficiency Medium Chain Acyl-Coenzyme A
Dehydrogenase Deficiency Menkes Disease Mental Retardation
Syndromes, Undiagnosed Metachromatic Leukodystrophy Metaphyseal
Chondrodysplasia, Schmid Type Mevalonicaciduria Mitochondrial
Disorders Chorea and Dementia Chronic Progressive External
Ophthalmoplegia Diabetes and Hearing Loss Infantile Myopathy and
Lactic Acidosis (Fatal and Non-Fatal Forms) Kearns-Sayre Syndrome
Leber Hereditary Optic Neuropathy Leigh Syndrome (mtDNA mutation)
MELAS MERRF NARP Nonsyndromic Hearing Loss and Deafness
Aminoglycoside-Induced Deafness Pearson Syndrome Molybdenum
Cofactor Deficiency MTHFR Deficiency Mucolipidosis I Mucolipidosis
II
Mucolipidosis IV Mucopolysaccharidosis Type I Mucopolysaccharidosis
Type II Mucopolysaccharidosis Type IIIA Mucopolysaccharidosis Type
IIIB Mucopolysaccharidosis Type IIIC Mucopolysaccharidosis Type
IIID Mucopolysaccharidosis Type IVA Mucopolysaccharidosis Type IVB
Mucopolysaccharidosis Type VI Mucopolysaccharidosis Type VII
Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia
Type 2 Familial Medullary Thyroid Carcinoma Multiple Endocrine
Neoplasia Type 2A Multiple Endocrine Neoplasia Type 2B Multiple
Epiphyseal Dysplasia Myoclonic Epilepsy of Unverricht and Lundborg
Myotonia Congenita, Dominant Myotonic Dystrophy Myotonic Dystrophy
Type 1 Myotonic Dystrophy Type 2 Myotubular Myopathies Myotubular
Myopathy, Dominant Myotubular Myopathy, Recessive Myotubular
Myopathy, X-Linked Myotubular Myopathy Type 1 Narcolepsy
Nephrogenic Diabetes Insipidus Nephrogenic Diabetes Insipidus,
Autosomal Nephrogenic Diabetes Insipidus, X-Linked Nephronophthisis
Nephronophthisis, Adolescent Nephronophthisis, Infantile
Nephronophthisis, Juvenile Netherton Syndrome Neurofibromatosis 1
Neuronal Ceroid-Lipofuscinoses Neuronal Ceroid-Lipofuscinosis,
Adult Neuronal Ceroid-Lipofuscinosis, Infantile Neuronal
Ceroid-Lipofuscinosis, Juvenile Neuronal Ceroid-Lipofuscinosis,
Late Infantile Neuronal Ceroid-Lipofuscinosis, Late Infantile
Neuronal Ceroid-Lipofuscinosis, Finnish Variant Neuronal
Ceroid-Lipofuscinosis, Gypsy/Indian, Early Juvenile Variant
Neuronal Ceroid-Lipofuscinosis, Turkish variant Northern Epilepsy
Neutrophil Antigen Genotyping Nevoid Basal Cell Carcinoma Syndrome
Niemann-Pick Disease Due to Sphingomyelinase Deficiency
Niemann-Pick Disease Type A Niemann-Pick Disease Type B
Niemann-Pick Disease Type C Niemann-Pick Disease Type C1
Niemann-Pick Disease, Nova Scotia Type Niemann-Pick Disease Type C2
Nijmegen Breakage Syndrome Non-Ketotic Hyperglycinemia
Nonepidermolytic Palmoplantar Hyperkeratosis Noonan Syndrome
Oculopharyngeal Muscular Dystrophy Organic Acidemias
3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Glutaricacidemia Type 1
Isovaleric Acidemia Ketothiolase Deficiency Maple Syrup Urine
Disease Maple Syrup Urine Disease Type 1A Maple Syrup Urine Disease
Type 1B Maple Syrup Urine Disease Type 2 Methylmalonic Aciduria
Methylmalonic Acidemia cb1C Variant Propionic Acidemia Ornithine
Transcarbamylase Deficiency Osteogenesis Imperfecta Type I
Osteogenesis Imperfecta Type II Osteogenesis Imperfecta Type III
Osteogenesis Imperfecta Type IV Osteopetrosis, Autosomal Dominant,
Type II Pachyonychia Congenita Paget Disease of Bone
Pallidopontonigral Degeneration; PPND Papillary Renal Carcinoma
Paraganglioma Parkin Type of Juvenile Parkinson Disease Periodic
Paralyses Hyperkalemic Periodic Paralysis Hypokalemic Periodic
Paralysis Hypokalemic Periodic Paralysis Type 1 Hypokalemic
Periodic Paralysis Type 2 Potassium-Sensitive Cardiodysrhythmic
Type Periodic Paralysis Periodontitis Peroxisomal Bifunctional
Enzyme Deficiency Phosphoglycerate Kinase Deficiency
Phosphoglycerate Mutase Deficiency Phosphorylase Kinase Deficiency
of Liver and Muscle Platelet Antigen Genotyping PLOSL Polycystic
Kidney Disease Polycystic Kidney Disease, Autosomal Dominant
Polycystic Kidney Disease 1, Autosomal Dominant Polycystic Kidney
Disease 2, Autosomal Dominant Polycystic Kidney Disease 3,
Autosomal Dominant Polycystic Kidney Disease, Autosomal Recessive
Porphyria Cutanea Tarda Potocki-Shaffer Syndrome Prader-Willi
Syndrome Preeclampsia Primary Pulmonary Hypertension Prion
Disorders Creutzfeldt-Jakob Disease Familial Fatal Insomnia
Gerstmann-Straussler Disease Progressive Familial Intrahepatic
Cholestasis Progressive Familial Intrahepatic Cholestasis 1
Progressive Familial Intrahepatic Cholestasis 2 PROP 1-Related
Combined Pituitary Hormone Deficiency Proximal Renal Tubular
Acidosis with Ocular Abnormalities Pseudoachondroplasia
Pseudoneonatal Adrenoleukodystrophy Pseudovitamin D Deficiency
Rickets Pseudoxanthoma Elasticum Pulmonary Surfactant Protein B
Deficiency Pycnodysostosis Pyridoxine-Dependent Seizures
Pyruvoyltetrahydropterin Synthase Deficiency Red Cell Antigens
Duffy Antigen Genotyping Kell Antigen Genotyping Kidd Genotyping M
Antigen Genotyping Rh C Genotyping Rh D Genotyping Rh E Genotyping
S Antigen Genotyping Retinitis Pigmentosa Retinitis Pigmentosa,
Autosomal Dominant Retinitis Pigmentosa, Autosomal Recessive
Retinitis Pigmentosa, Autosomal Recessive, Bothnia Type Retinitis
Pigmentosa, X-Linked Retinoblastoma Rett Syndrome Rhizomelic
Chondrodysplasia Punctata Rhizomelic Chondrodysplasia Punctata Type
1 Rhizomelic Chondrodysplasia Punctata Type 2 Rhizomelic
Chondrodysplasia Punctata Type 3 Rod Monochromacy Rothmund-Thomson
Syndrome Russell-Silver Syndrome Saethre-Chotzen Syndrome Salla
Disease Sclerosteosis Sex-Determining Region Y Short Chain
3-Hydroxyacyl-CoA Dehydrogenase Deficiency, Short Chain Acyl-CoA
Dehydrogenase Deficiency Short Stature Shox Deficiency
Simpson-Golabi-Behmel Syndrome Sitosterolemia Sjogren-Larsson
Syndrome Smith-Magenis Syndrome Specialized Cytogenetics Services
Telomere Analysis X Inactivation Studies Spinal and Bulbar Muscular
Atrophy Spinal Muscular Atrophy Arthrogryposis multiplex congenita
Congenital axonal neuropathy Spinal Muscular Atrophy I Spinal
Muscular Atrophy II Spinal Muscular Atrophy III Spinal Muscular
Atrophy IV Spinal Muscular Atrophy with Respiratory Distress 1
Split-Hand/Foot Malformation, Type 4 Spondyloepimetaphyseal
Dysplasia, Strudwick Type Spondyloepiphyseal Dysplasia Tarda,
X-Linked Steatocystoma Multiplex Succinic Semialdehyde
Dehydrogenase Deficiency Sulfatidosis, Juvenile, Austin Type
Thanatophoric Dysplasia Type I Thanatophoric Dysplasia Type II
Thrombophilia Factor V Leiden Thrombophilia Factor V R2 Mutation
Thrombophilia MTHFR Thermolabile Variant Prothrombin G20210A
Thrombophilia Thyroid Hormone Resistance Townes-Brocks Syndrome
Transthyretin Amyloidosis Familial Amyloid Cardiomyopathy Familial
Amyloid Polyneuropathy Type 1 (Portuguese-Swedish-Japanese type)
Familial Amyloid Polyneuropathy Type II (Indiana/Swiss or
Maryland/German type) Familial Oculoleptomeningeal Amyloidosis
Leptomeningeal Amyloidosis Trichorhinophalangeal Syndrome Type I
Trichothiodystrophy Tuberous Sclerosis Complex Tuberous Sclerosis I
Tuberous Sclerosis II Type II Collagenopathies Achondrogenesis Type
II Kniest Dysplasia Spondyloepiphyseal Dysplasia Spondyloepiphyseal
Dysplasia, Congenita Stickler Syndrome Type I Tyrosinemia Type I
Tyrosinemia Type II Uniparental Disomy Testing, General van Buchem
Disease Variegate Porphyria Very Long Chain Acyl-CoA Dehydrogenase
Deficiency Vohwinkel Syndrome Von Hippel-Lindau Syndrome Von
Willebrand Disease Von Willebrand Disease Type 2A Von Willebrand
Disease Type 2B Von Willebrand Disease Type 2M Von Willebrand
Disease Type 2N (Normandy) White Sponge Nevus of Cannon Williams
Syndrome Wilson Disease Wiskott-Aldrich Syndrome Wolf-Hirschhorn
Syndrome Wolman Disease X-Linked Adrenal Hypoplasia Congenita
X-Linked Agammaglobulinemia Xeroderma Pigmentosa Y Chromosome
Deletion Sertoli Cell Only Syndrome Y Chromosome
Detection/Molecular Genetics Zellweger syndrome Zonular Pulverulent
Cataract
EXAMPLE 2
Integrated Instrument to Obtain Informed Consent for Genetic Tests
for Cystic Fibrosis
Genetic testing for cystic fibrosis is now recommended for all
Caucasian couples anticipating childbearing. There are currently
.about.4 million pregnancies/year. Laws in several states require
that informed consent be obtained for all genetic tests. Most
primary care physicians and OB/GYNs have little training in
genetics and limited ability to provide information and instruction
to patients concerning genetic tests for cystic fibrosis, the
utility and interpretation of test results, the procedures
governing genetic testing and genetic information, the social,
medical, and psychological implications of testing, and the balance
of risk and benefit involved in having such tests performed. The
instruments and methods described in this invention enable
healthcare practitioners with little training or knowledge of
genetics to obtain a meaningful informed consent using validated
and integrated elements for providing information and instruction
to individuals, collecting a personal medical and family history,
assessing the individual's retention and comprehension of
information concerning the genetic test, certifying the
individual's consent for the test, establishing a proper medical
record, and properly processing the sample.
The integrated instrument contains an instruction element which
includes stepwise directions to the practitioner in the process of
obtaining an informed consent and provides text and illustrative
materials that the practitioner can use to explaining the test, the
test procedures, and its consequences to the individual. The
instrument also to contains text and illustrative materials
designed for individuals that constitutes a reliable and
understandable source of information about the test. A collection
element constitutes a worksheet that can be used by the
practitioner and individual to construct a personal medical and
family history. The worksheet contains specific questions about the
individual's racial make-up, and the racial make-up of the
individuals family (siblings, parents, siblings of the parents,
grandparents and siblings of the grandparents, and so on), the
individual's health status and the health status and history of the
individual's family. An assessment element enables the provider to
assess the individual's retention of information. It comprises a
series of questions about the reasons for the test, the test
procedures, the possible test results and the meaning of the test
results and basic question about cystic fibrosis. The certification
element enables the individual to indicate their permission for
testing to be performed and for this permission to be witnessed, it
includes a written document that states that the individual has
reviewed and understands the information transmitted in the
information element and includes blank signature lines for the
individual's signature, and the signatures of the practitioner and
the witness. Other elements assist in establishing a medical
record, labeling the sample, and billing for the cost of the test.
The instrument is validated through clinical trials which establish
that the language comprising the information element and the
procedures established in the instruction element are effective in
establishing the requisite level of understanding required for an
individual to provide a valid informed consent. Table I below sets
forth the contents of an exemplary informed consent instrument for
Cystic Fibrosis testing.
EXAMPLE 3
Integrated Instrument to Obtain Informed Consent for Genetic Tests
for Alzheimer's Disease
Genetic testing for genes involved in Alzheimer's Disease can be
performed for individuals with early symptoms of dementia or
asymptomatic individuals with a family history of the disease.
While Alzheimer's Disease is highly genetic (i.e., it exhibits high
heritability) it is also polygenic, meaning many different genes
may be involved in its etiology. Genetic tests for variances in
apolipoprotein E (apoE4) are associated with a more rapid
progression of Alzheimer's disease, and variations in the genes for
amyloid precursor protein, antichymotrypsin, and presenillin have
also been associated with the disease. The genetics of the disease
and determinations of risk based on family history and genetic test
results currently requires specialized training in genetics. Most
primary care physicians do not have the training to instruct
patients in the genetics of Alzheimer's Disease, use of genetic
information to assess their risk of Alzheimer's Disease the social,
medical, and psychological implications of testing, and the balance
of risk and benefit involved in having such tests performed.
The instruments and methods described in this invention enable
healthcare practitioners with little training or knowledge of
genetics to obtain a meaningful informed consent using validated
and integrated elements for providing information and instruction
to individuals, collecting a personal medical and family history,
assessing the individual's retention and comprehension of
information concerning the genetic test, certifying the
individual's consent for the test, establishing a proper medical
record, and properly processing the sample. These elements comprise
a booklet with information about Alzheimer's Disease and the role
of genetic testing written at an 8.sup.th grade level for the
patients and give the practitioner stepwise directions and explicit
language to use in explaining the genetics of Alzheimer's Disease,
diagrams illustrating the natural course of early and late forms of
Alzheimer's Disease and the characteristic patterns of inheritance
of polygenetic disorders, as well as reference information and
answers to frequently asked questions. The instrument also helps
the practitioner collect a family history and provides a worksheet
that can be used to make a quantitative assessment of genetic risk
based on this history. These elements are validated through
clinical trials which establish that the language comprising the
information element and the procedures established in the
instruction element are effective in establishing the requisite
level of understanding required for an individual to provide a
valid informed consent. Other elements help the provider to assess
the individual's retention of information, enable the individual to
certify their consent, establish a medical record, label the
sample, and arrange payment for the test. Table II below sets forth
the contents of an exemplary informed consent instrument for
Alzheimer's Disease risk.
EXAMPLE 4
Integrated Instrument to Obtain Informed Consent for Genetic Tests
for Risk of Stroke
Stroke and other symptomatic manifestations of cardiovascular
disease can be caused by several different genetic variations.
These different forms of cardiovascular disease may require
different therapies. For example, variances in apolipoprotein E,
LDL, or LDL-R can lead to increased levels of cholesterol and
require therapy with diet and drugs aimed at lowering cholesterol.
Variances in methylenetetrahydrofolatereductase may increase levels
of homocysteine and require therapy with diet and folate aimed at
lowering cholesterol. Variances in the angiotensinogen gene may
lead to cardiovascular disease due to imbalances of salt and
require therapy with diet, salt restriction, or diuretics aimed at
reducing the salt load. Variances in genes involved in the clotting
cascade, particularly factor V, may predispose to blood clots and
stroke which may be treated with anti-coagulants and
anti-thrombotics. Other genetic tests for cardiovascular disease
are currently in research and development. To provide informed
consent for such tests, the practitioner reviews the patient's
family history to make a preliminary calculation of genetic risk
and identify likely candidates for such risk (e.g. history of high
cholesterol or thrombosis). Based on this information the
practitioner may recommend one for more genetic tests that could be
used to customize measures to prevent cardiovascular disease and
stroke. Most primary care physicians do not have the sufficient
training or knowledge of recent developments in cardiovascular
genetics to make such determinations and counsel patients in the
potential use of genetic information in the prevention of
cardiovascular disease.
The instruments and methods described in this invention enable
healthcare practitioners with little training or knowledge of
genetics to obtain a meaningful informed consent using validated
and integrated elements for providing information and instruction
to individuals, collecting a personal medical and family history,
assessing the individual's retention and comprehension of
information concerning the genetic test, certifying the
individual's consent for the test, establishing a proper medical
record, and properly processing the sample. These elements comprise
a booklet with information about the genetic and non-genetic
factors that contribute to stroke written at an 8.sup.th grade
level for the patients and give the practitioner stepwise
directions and explicit language to use in explaining the genetics
of stroke, diagrams illustrating the different factors that
contribute to stroke, as well as reference information and answers
to frequently asked questions. The instrument also helps the
practitioner collect a family history and provides a worksheet that
can be used to make a quantitative assessment of genetic risk based
on this history. These elements are validated through clinical
trials which establish that the language comprising the information
element and the procedures established in the instruction element
are effective in establishing the requisite level of understanding
required for an individual to provide a valid informed consent.
Other elements help the provider to assess the individual's
retention of information, enable the individual to certify their
consent, establish a medical record, label the sample, and arrange
payment for the test. The method comprises procuring a booklet that
comprises the instrument. The information element is separated from
the booklet and given to the patient. The practitioner follows
directions in the instruction element to guide the patient through
information concerning the ethology of stroke, genetic tests that
may be useful in identifying genetic risk factors for stroke, and
the process and consequences of performing a test. The practitioner
uses a check list to indicate the completion of each step of the
process. The practitioner then uses the collection element to
collect a personal family and medical history and a worksheet
within this element to make a determination of the patient's
genetic risk. An assessment of the patient's retention and
understanding of the information is made using the assessment
instrument, and, when an acceptable level of understanding is
demonstrated, the patient signs an informed consent form with
witnesses from the certification element according to directions in
the instruction element. Carbon copies of the checklist,
assessment, and certification are made onto a recording element
coincident with the original signatures, and this element is placed
in the patient's medical record as described in the instruction
element. The sample is labeled with an adhesive backed label that
is separated from the back cover of the instrument as described in
the instruction element, and the invoice is separated from the
instrument and given to the patient. Table III sets forth the
contents of an exemplary informed consent instrument for genetic
risk of stroke.
EXAMPLE 5
Integrated Instrument to Obtain Informed Consent for
Pharmagenogenetic Testing
Genetic variation in genes that are responsible for drug metabolism
may alter the safety and efficacy of these medications for an
individual. These tests may, for example, identify individuals who
are refactory to the pain-killing effects of codeine, individuals
who are at risk from undue toxicity from various neuro-psychiatric
drugs, and individuals who are at risk of abnormally high levels of
warfarin. CYP2D6 and CYP3C9 are two examples of genes that may be
tested to help guide the choice of pharmaceutical therapy. Genetic
tests for pharmacogenetic testing will commonly be performed by the
prescribing physician who may have little or no training in
genetics and in situations where professional genetics support may
not be available. While the genetic predisposition to adverse drug
events or drug resistance may not raise some of the ethical issues
that surround genetic tests for disease predisposition, informed
consent is, nevertheless, necessary regarding issues such as sample
handling, DNA banking, and the privacy of genetic records.
Accordingly, physicians need to have an effective method for
providing individuals with information concerning the test, how the
test results can be used, and how follow-up may be maintained,
instructing the individual concerning the handling of the sample
and information from the genetic test, and obtaining a valid
informed consent.
The instruments and methods described in this invention enable
healthcare practitioners with little training or knowledge of
genetics to obtain a meaningful informed consent using validated
and integrated elements for providing information and instruction
to individuals. These elements comprise a booklet with information
about genetic effects on drug action and the process of genetic
testing written at an 8.sup.th grade level for the patients and
give the practitioner stepwise directions and explicit language to
use in explaining how this information could be used to improve the
choice of the medication and the dose that will be prescribed. The
instrument also contains an assessment to determine the
individual's comprehension and retention of information concerning
the test and testing procedures. These information element and
instruction element also contain materials relating to a follow-up
service through which individuals are contacted with regular
updates concerning new medications and how these medications are
affected by genetic variations. Individuals are asked to indicate
their consent for such contacts by the service or to formally
reject such contacts in the certification element. The choice
whether or not to participate in the follow-up program is also
noted in the recording element. If the individual chooses to
participate, this element will also include contact information for
such follow-up and copies of this element will be recorded
automatically with the follow-up service. The billing element is
used to pay both for the genetic tests that are to be performed and
for an initial subscription to this service. Also included in the
instrument are elements for labeling of the sample. Table IV below
sets forth the contents of an exemplary informed consent instrument
for pharmacogenetic testing.
REFERENCES
Code Of Federal Regulations--.sctn.46.116, 46.117 Elias S, Annas G
J. Generic consent for genetic screening. N Engl J Med 1994;
330:1611-1613 Andrews L B, Fullarton J E, Holtsman N A, Motuisky A
G, eds. Assessing genetic risks: implications for health and social
policy. Washington, D.C.: National Academy Press, 1994 Ciske D J,
Haavisto A, Laxova A, Rock L Z, Farrell P M. Genetic counseling and
neonatal screening for cystic fibrosis: an assessment of the
communication process. Pediatrics April 2001; 107(4):699-705
Andrews L B., Compromised consent: deficiencies in the consent
process for genetic testing. J Am Med Womens Assoc 1997 Winter;
52(1):39-42 Hofman K J, Tambor E S, Chase G A, Geller G, Faden R R,
Holtzman N A., Physicians' knowledge of genetics and genetic tests.
Acad Med August 1993; 68(8):625-32 Cho M K, Arruda M, Holtzman N
A., Educational material about genetic tests: does it provide key
information for patients and practitioners? Am J Med Genet Dec. 19,
1997; 73(3):314-20 Robertson J A., Consent and privacy in
pharmacogenetic testing. Nat Genet July 2001; 28(3):207-9 Geller G,
Strauss M, Bernhardt B A, Holtzman N A., "Decoding" informed
consent. Insights from women regarding breast cancer susceptibility
testing. Hastings Cent Rep, March-April 1997; 27(2):28-33 Rieger P
T, Pentz R D., Genetic testing and informed consent. Semin Oncol
Nurs May 1999; 15(2): 104-15 U.S. Pat. No. 6,149,440 entitled
Methods and Apparatus for Authenticating Informed Consent U.S. Pat.
No. 5,999,909 entitled Methods for Establishing a Certifiable
Informed Consent For A Procedure U.S. Pat. No. 5,799,282 entitled
Methods for Establishing Certifiable Informed Consent For A Medical
Procedure
TABLE-US-00004 TABLE I INFORMED CONSENT INSTRUMENT FOR CYSTIC
FIBROSIS TESTING INSTRUCTION ELEMENT Instructions for obtaining
informed consent with this product Checklist (WORKSHEET)
INFORMATION ELEMENT Instructions to be provided to individuals
ASSESSMENT ELEMENT What is cystic fibrosis? (PRINTED MATERIALS/
Instructional materials on cystic fibrosis 1 Which of the following
is not true about CF? VIDEO PRESENTATION) (a) CF affects the lungs
and digestive system (b) CF is caused by mutations in the CFTR gene
(c) there is no treatment for CF (d) CF can cause mild disorders
including sterility and chronic sinusitus (e) CF can cause
premature death due to lung disease Characteristics of the disease
Describing the characteristics of the disease CFTR - the "CF gene"
Describing the biological basis of cystic fibrosis (WITH DIAGRAM)
How is cystic fibrosis inherited? Describing the inheritance of
cystic fibrosis 2 Which of the following describes the inheritance
of CF (a) affected individuals have only one mutant gene which is
inherited from the father (b) affected individuas have only one
mutant gene which is inherited from the mother (c) cystic fibrosis
is caused by an infection with bacteria or viruses (d) affected
individuals have two mutant genes. one inherited from each parent
Genetic tests for cystic fibrosis Describing mutations in the CFTR
gene and genetic tests 3. Which of the following is not true of a
carrier of CF? (a) carriers are unaffected by cystic fibrosis (b)
all of the children of a carrier will be affected with cystic
fibrosis (c) on average, 1/4 children of two carriers will be
affected with cystic fibrosis (d) on average, 1/2 children of one
carrier will also be carriers (e) approximately 1/20 caucasians are
carriers What does it mean if I have a gene for cystic fibrosis? 4.
Which of the following statements are not true? (a) variations in
the CFTR gene are the cause of cystic fibrosis (b) approximately
1/20 caucasians are carriers of cystic fibrosis (c) there are fewer
carriers of the cystic fibrosis gene among non-caucasians (d)
cystic fibrosis never occurs among non-caucasians (e) cystic
fibrosis is less common among non-caucasians (f) genetic testing is
available to anyone without regard to their race or ancestory
Carriers have one mutant gene and one normal gene Describing the
carrier status for CF Affected individuals have two mutant genes
Differentiating carriers from affected individuals What is the
treatment for cystic fibrosis? Instructional materials on the
management of cystic fibrosis 5 Which of the following statements
are not true? (a) early diagnosis and therapy in the newborn period
may improve outcome (b) children with CF may suffer from
malnutrition and poor growth (c) enzyme and nutritional therapy can
restore normal growth (d) treatment with antibiotics can preserve
lung function (e) gene therames to fix the CFTR gene will be
approved soon Professional healthcare and health management
Describing the role of health care professionals 6 Which of the
following statements are not true? (a) genetic testing can aid
early diagnosis and treatment of affected children (b) prenatal
diagnosis is available to parents who are known to be carriers (c)
abortion is recommended if a child is diagnosed with cystic
fibrosis (d) early diagnosis and treatment of newborns with cystic
fibrosis is recommended (e) two carriers planning a pregnancy
should consult with a CF specialist Preventing and treating
nutritional problems Describing enzyme and nutritional management
Preventing and treating lung disease Describing pulmonary
management Long term prognosis and quality of life Describing
prognosis for cystic fibrosis Preconception and reproductive
planning Describing prenatal diagnosis and reproductive planning
How is the genetic test performed? Instructional materials on how
genetic tests are performed What is informed consent? Describing
the purpose and regulations regarding informed 7 Which of the
following statements is not true? consent (a) genetic testing can
not be performed wihtout your consent (b) samples are used only for
the purpose described in the consent (c) samples can be sold for
research without your consent (d) samples can be saved for
additional testing in the future (e) a health professional in the
laboratory will check the test results (f) it is recommended to
meet with a provider to review test results (g) your medical
records can not be sent to anyone without consent How do I provide
a sample for testing? Describing the testingprocess How is this
sample handled? What happens to the Describing sample handing
procedures sample after the test is completed? Who performs the
test? Describing sample testing procedures Who receives the test
results? Describing policies regarding medical record privacy and
distribution Does anyone else have to know the test results? How
will I know what to do when I receive the test Describe the
follow-up process results? What is genetic counseling? Describe
genetic counseling and referral procedures What does my medical
history and family history Instructions on completing medical
history and tell me about my risk? family history Should I have
this test performed? Guiding the individual's choice whether or not
to 8 Which of the following statements is not true? perform a test
(a) You are more likely to be a carrier if someone in your family
has cystic fibrosis (b) You are more likely to be a carrier if
someone else in your family is also a carrier (c) You may carry a
CF gene even if no one in your family has ever had the disease (d)
all of the mutations that cause CF can be detected by genetic
testing (e) more than 97% of the mutaitons that cause CF can be
detected by genetic testing (f) genetic testing can be performed
before birth through CVS or amniocentesis (g) generally a child
will be affected with CF only if both parents are carriers Does my
family history suggest I have an increased Instructions on
calculating risk from family history risk? Recommendations of
experts in the field. Recommendations of the NIH and professional
societies 9 Which of the following statements are true? (a) genetic
testing for carriers of CF is performed at birth by the public
health service (b) the NIH recommends genetic testing for all
caucasian couples before childbearing (c) genetic testing for
cystic fibrosis is required by the government and health plans (d)
carriers should not have children because they may have cystic
fibrosis Should my family members be tested also? Guding a
discussion on whether to discuss test with family members What are
the benefits of performing this genetic test? Describing the
benefits of identifying genetic risk factors What are the risks of
performing this genetic test? Describing the risks of identifying
genetic risk factors 10 Which of the following are not prohibited
by law? (a) hiring or firing based on a genetic test result (b)
denying health insurance or health care based on a genetic test (c)
performing a genetic test without an individuals consent (d) giving
test results to employer without an individuals consent (e) keening
test results secret from employers family or friends Do I want to
know this information? Describing emotional and practical
implications of identifying risk factors Will I act on this
information? Will a positive test affect my ability to get a job?
Describing laws against discrimination and nationwide experience
Will a positive test affect my ability to get health Describing
laws against discrimination insurance? Will a positive test affect
my ability to get life Discussing potential impact on life
insurance insurance? What does it cost? Pricing and reimbursement
issues Instruction on self-assessment Instructions for performing
assessment. Instructions on completing informed consent
Instructions for completing informed consent Instructions for
providing a sample Instructions for obtaining sample Instructions
for labeling sample Is this test covered by my insurance?
Instructions for self-payment or reimbursement Should I pay for
this directly? Should I claim reimbursement? Instructions for
completing medical record Who to contact for more information
Additional instructional materials Test results Background on
informed consent Referalls to health care providers Background
information on patterns of inheritance (WITH DIAGRAM) Background
information on genes, DNA, chromosomes (WITH DIAGRAM) Background
information on cardiovascular system (WITH DIAGRAM) Background on
psychosocial issues in genetic testing Background on the potential
for genetic discrimination Answers to frequently asked questions
CERTIFICATION ELEMENT RECORDING ELEMENT COLLECTION ELEMENT
Checklist LABELING ELEMENT BILLING ELEMENT Checklist Qustion 1
result Qustion 1 result Question 2 result Question 2 result
Question 3 result Question 3 result Question 4 result Question 4
result Question 5 result Question 5 result Qudestion 6 result
Qudestion 6 result Question 7 result Question 7 result Medical and
Family History Worksheet Subjective assessment of healthcare
concerns Personal medical history Review of systems Family
tree/geneology Family medical history Qudstion 8 result Qudstion 8
result Question 9 result Question 9 result Qustion 10 result
Qustion 10 result Informed consent form Text Signature pages
(duplicate) Materials for labeling sample Personal
identification/deidentification Label to affix to sample Contact
information for reporting results Billing forms self pay forms
reimbursement claim forms Checklist for medical record assessment
medical history worksheet family history worksheet informed consent
(signed) contact information for reporting results
TABLE-US-00005 TABLE II INFORMED CONSENT INSTRUMENT FOR ALZHEIMER'S
DISEASE RISK INSTRUCTION ELEMENT Instructions for obtaining
informed consent with this product Checklist (WORKSHEET)
INFORMATION ELEMENT Instructions to be provided to individuals
ASSESSMENT ELEMENT What are the genes that affect my risk for AD?
Instructional materials on pathogenesis of Alzheimer's 1 Which of
the following is not true about Alzheimer's Disease? Disease (a) AD
involves the accumulation of amyloid proteins in the brain (b)
Dementia is a normal part of the aging process (c) AD is the most
common form of dementia (d) The onset of AD is often gradual (e)
Most individuals are diagnosed only when the disease is advances
(f) The mental deficits caused by AD are not reversible What do
these genes do? Describing the pathology of Alzheimer's Disease
(DIAGRAM) Describing the clinical course of Alzheimer's Disease
(CHARTS) How do variations in these genes increase my risk for
Describing the inheritance in Alzheimer's Disease 2 Genetic factors
account for what fraction of the risk of stroke? Alzheimer's
Disease? (a) 75-100% (b) 50-75% (c) 25-50% (d) less than 25% (e)
none What risk factors can be determined through genetic tests?
Describing the role of specific genes that can be tested 3 Which of
the following genes may be associated with AD? (a) apolipoprotein E
(ApoE) (b) Amyloid precursor protein (c) Presenillin (d)
antichymotrypsin (e) all of the above What does it mean if I have
genes that increase my risk 4 Which of the following statements are
not true? of AD (a) rare cases of AD are due to severe mutations in
single genes (b) most cases are multifactorial or involve multiple
genes (c) a positive ApoE test does not mean I will definitely have
AD (d) a negative ApoE test means I will definitely not get AD (e)
genetic tests may predict the effective of drugs for AD (f) family
history is an important medicine of AD risk In rare families, AD is
inherited in a predictably genetic manner In most families, AD is
considered to be multifactorial or ApoE associated with many genes
The effect of ApoE Amyloid Precursor Protein Other genes that may
be involved in Alzheimer's Disease Presenillin Amyloid precursor
protein (APP) Presenillin Antichymo- trypsin Antichymotrypsin The
effect of combinations of genes Ongoing research in genetics of
Alzheimer's Disease Can I do anything to prevent AD if tests show
that I am at Instructional materials on responding to the risk of
Alzheimer's 5 Which of the following statements are not true? risk?
Disease (a) there are no approved drugs for treating or preventing
AD (b) cholinesterase inhibitors may slow progression of AD (c)
anti-inflammatory drugs may help prevent AD (d) St. Johns Wart has
no proven effect on AD (e) anti-oxidant drugs may help prevent AD
(f) behavioral therapy may benefit individuals with AD Professional
healthcare and health management. Describing the role of health
care professionals 6 Which of the following statements are not
true? (a) genetic testing can help people cope with the risk of AD
(b) genetic testing can lead to earlier use of drugs to slow AD (c)
genetic tests today can lead to effective prevention of AD (d)
follow-up by health professionals is an important part of AD care
Approved drugs delay onset of disease Describing effect of
cholinesterase inhibitors (Tacrine, Ancept, others) Other drugs are
being studied in clinical trials Clinical experience and trials
with anti-infalmmatory drugs What kind of follow-up and care is
available? Clinical exerience and trials with estrogen Clinical
experience and trials with antioxidants + D11 Clinical experience
and trials with alternative medicines How is the genetic test
performed? Instructional materials on how genetic tests are
performed What is informed consent? Describing the purpose and
regulations regarding informed 7 Which of the following statements
is not true? consent (a) genetic testing can not be performed
without your consent (b) samples are used only for the purpose
described in the consent (c) samples can be sold for research
without your consent (d) samples can be saved for additional
testing in the future (e) a health professional in the laboratory
will check the test results (f) it is recommended to meet with a
provider to review test results (g) your medical records can not be
sent to anyone without consent How do I provide a sample for
testing? Describing the testingprocess How is the sample handled?
What happens to the sample Describing sample handing procedures
after the test is completed? Who performs the test? Describing
sample testing procedures Who receives the test results? Describing
policies regarding medical record privacy and distribution Does
anyone else have to know the test results? How will I know what to
do when I receive the test Describe the follow-up process results?
What is genetic counseling? Describe genetic counseling and
referral procedures Should I have this test performed? Guiding the
individual's choice whether or not to per- 8 Which of the following
statement is not true? form a test (a) If one or more family
members have AD. you have increased risk (b) If your father or
mother had AD, your risk of AD is >50% (c) Genetic tests can not
identify all of the risk factors for AD (d) Variation in ApoE may
increase the rate of progression of AD (d) I can be at risk for AD
even without a family history of AD (f) I can be at risk for a AD
even if these tests come back normal Does my medical history
suggest I have an increased risk Instructions on taking a medical
history (WORKSHEET) Does my family history suggest I have an
increased risk? Instructions on taking a family history (WORKSHEET)
Recommendations of experts in the field Recommendations of the NIH
and professional societies Should my family members be tested also?
Guding a discussion on whether to discuss test with family members
What are the benefits of performing this genetic test? Describing
the benefits of identifying genetic risk factors Early detection
and prevention of cardiovascular disease 9 Which of the following
statements are true? (a) genetic testing is recommended for
everyone to prevent AD (b) genetic tests are not recommended
without symptoms of AD (c) a negative genetic test will tell me I
am not ar risk for AD (d) treatments have been shown to effectively
prevent most AD (e) there are no treatments to slow the progression
of AD What are the risks of performing this genetic test?
Describing the risks of identifying genetic risk factors 10 Which
of the following are not prohibited by law? (a) hiring or firing
based on a genetic test result (b) denying health insurance or
health care based on a genetic test (c) performing a genetic test
without an individuals consent (d) giving test results to employer
without an individuals consent (e) keening test results secret from
employers family or friends Do I want to know this information?
Describing emotional and practical implications of identifying risk
factors Will a positive test affect my ability to get a job?
Describing laws against discrimination and nationwide experience
Will a positive test affect my ability to get health Describing
laws against discrimination insurance? Will a positive test affect
my ability to get life insurance? Discussing potential impact on
life insurance What does it cost? Pricing and reimbursement issues
Instructions on self-assessment Instructions for performing an
assessment Instructions on completing informed consent Instructions
for completing informed consent Instructions for providing a sample
Instructions for obtaining sample Instructions for labeling sample
Is this test covered by my insurance? Instructions for self-payment
or reimbursement Should I pay for this directly? Should I claim
reimbursement? Instructions for completing medical record Who to
contact for more information Additional instructional materials
Test results Background on informed consent Referalls to health
care providers Background information on patterns of inheritance
(WITH DIAGRAM) Background information on genes DNA. chromosomes
(WITH DIAGRAM) Background information on cardiovascular system
(WITH DIAGRAM) Background on psychosocial issues in genetic testing
Background on the potential for genetic discrimination Answers to
frequently asked questions CERTIFICATION ELEMENT RECORDING ELEMENT
COLLECTION ELEMENT Checklist LABELING ELEMENT BILLING ELEMENT
Checklist Question 1 result Question 1 result Question 2 result
Question 2 result Question 3 result Question 3 result Question 4
result Question 4 result Question 5 result Question 5 result
Question 6 result Question 6 result Question 7 result Question 7
result Question 8 result Question 8 result Medical and Family
History Worksheet Subjective assessment of healthcare concerns
Personal medical history Review of systems Family tree/geneology
Family medical history Question 9 result Question 9 result Qustion
10 result Qustion 10 result Informed consent form Text Signature
pages (duplicate) Materials for labeling sample Personal
identification/deidentification label to affix to sample Contact
information for reporting results Billing forms self pay forms
reimbursement claim forms Checklist for medical records assessment
medical history worksheet family history worksheet informed consent
(signed) contact information for reporting results
TABLE-US-00006 TABLE III INFORMED CONSENT INSTRUMENT FOR RISK OF
STROKE INSTRUCTION ELEMENT Instructions for obtaining informed
consent with this product Checklist (WORKSHEET) INFORMATION ELEMENT
Instructions to be provided to individuals ASSESSMENT ELEMENT What
are the genes that affect my risk for stroke? Instructional
materials on the pathogenesis of stroke 1 Which of the following is
not true about stroke? (a) stroke involves a temporary loss of
blood flow to part of the brain (b) strokes are generally
associated with diseases of blood vessels (c) strokes do not occur
in people less than 50 years of age (d) high blood pressure can
increase the risk of stroke (e) increased blood clotting can
increase the risk of stroke (e) the risk of stroke can be decreased
by lifestyle diet and drugs What do these genes do? Describing the
biological basis of stroke (WITH DIAGRAM) How do variations in
these genes increase my risk for Describing the role of genetics in
stroke 2 Genetic factors account for what fraction of the risk of
stroke? stroke? (a) 100% (b) more than 75% (c) 30-50% (d) less than
25% What risk factors can be determine through genetic tests?
Describing the role of specific genes that can be tested 3 Which of
the following genes may be involved in the risk of stroke? (a)
apolipoprotein E (ApoE( (b) methylenetetrahydrofolate reductase
(MTHFR) (c) blood clotting factors (factor V) (d) angiotensinogen
(e) all of the above What does it mean if I have genes that
increase my risk for 4 Which of the following statements are not
true? stroke? (a) all of the genes that predict the risk of stroke
are known (b) approximately 10% of normal people have variations in
MTHFR (c) complete genetic deficiency of LDL-R is very rare (d)
variations in angiotensinogen may lead to high blood pressure (e)
some variations in ApoE prevent stroke, others increase the risk
(f) genetic variations may increase the risk of blood clots in the
brain The effect of genes that predispose to high blood pressure
Angiotensinogen The effect of genes that predispose to blood
clotting Factor V, factor II The effect of genes that increase
cholesterol, ApoE, LDL-R, LPL, MTHFR homocysteine, or blood sugar
(diabetes) The effect of combinations of genes Describing polygenic
or multifactorial disease What can I do to prevent a stroke if the
test shows I Instricutional materials on options to reduce the risk
of stroke 5 Which of the following statements are not true? have an
increased risk? (a) lowering blood pressure reduces the risk of
stroke (b) lowering cholesterol and homocysteine reduces the risk
of stroke (c) treating diabetes early lowers the risk of stroke (d)
the genetic risk of stroke can not be reduced by diet or drugs (e)
the risk of stroke is related to several genes diet and lifestyle
Professional healthcare and health management Describing the role
of health care professionals 6 Which of the following statements
are not true? (a) dietary changes can lower cholesterol and the
risk Of stroke (b) a diet rich in folate and vitamin B12 may reduce
the risk of stroke (c) drugs that lower cholesterol may reduce the
risk of stroke (d) anyone at risk for stroke should take drugs to
inhibit blood clotting (e) controlling diabetes reduces the risk of
stroke Lifestyle changes Describing the role of lifestyle changes
Dietary changes and supplements Describing dietary restriction and
supplements Drugs to control blood pressure Describing the
treatment of elevated blood pressure Drugs to control cholesterol
and triglycerides Describing the treatment of elevated cholesterol
and triglycerides Drugs to prevent blood clots Describing drugs to
prevent thrombosis Preventing and treating diabetes Describing the
diagnosis and treatment of diabtestes How is the genetic test
performed? Instructional materials on how genetic tests are
peformed What is informed consent? Describing the purpose and
regulations regarding informed 7 Which of the following statements
is not true? consent (a) genetic testing can not be performed
without your consent (b) samples are used only for the purpose
described in the consent (c) samples can be sold for research
without your consent (d) samples can be saved for additional
testing in the future (e) a health professional in the laboratory
will check the test results (f) it is recommended to meet with a
provider to review test results (g) your medical records can not be
sent to anyone without consent How do I provide a sample for
testing? Describing the testingprocess How is this sample handled?
What happens to the sample Describing sample handing procedures
after the test is completed? Who performs the test? Describing
sample testing procedures Who receives the test results? Describing
poicies regarding medical record privacy and distribution Does
anyone else have to know the test results? How will I know what to
do when I receive the test Describe the follow-up process results?
What is genetic counseling? Describe genetic counseling and
referral procedures Should I have this test performed? Guiding the
individual's choice whether or not to perform a test 8. Which of
the following statement is not true? (a) If two or more family
members had strokes, you have increased risk (b) If your father or
mother had a stroke, your risk of a stroke is >90% (c) Genetic
tests can not identify all of the risk factors for stroke (d)
Variation in ApoE, MTHFR, or fator V can increase the risk of
stroke (e) I can be at risk for stroke even without a family
history of stroke (f) I can be at risk for a stroke even if these
tests come back normal Does my medical history suggest I have
increased risk Instructions on taking a medical history (WORKSHEET)
Does my family history suggest I have an increased risk?
Instructions on taking a family history (WORKSHEET) Recommendations
of experts in the field. Recommendations of the NIH and
professional societies Should my family members be tested also?
Guding a discussion on whether to discuss test with family members
What are the benefits of performing this genetic test? Describing
the benefits of identifying genetic risk factors Early detection
and prevention of cardiovascular disease 9 Which of the following
statments are true? (a) genetic testing is recommended for everyone
to prevent storke (b) genetic tests identify all of the risk
factors for stroke (c) genetic testing can be used to help reduce
the risk of stroke (d) genetic testing can tell me if I am not ar
risk for a stroke (e) genetic testing is essential to prevent
stroke What are the risks of performing this genetic test?
Describing the risks of identifying genetic risk factors 10 Which
of the following are not prohibited by law? (a) hiring or firing
based on a genetic test result (b) denying health insurance or
health care based on a genetic test (c) performing a genetic test
without an individuals consent (d) giving test results to employer
without an individuals consent (e) keening test results secret from
employers family or friends Do I want to know this information?
Describing emotional and practical implications of identifying risk
factors Will a positive test affect my ability to get a job?
Describing laws against discrimination and nationwide experience
Will a positive test affect my ability to get health Describing
laws against discrimination insurance? Will a positive test affect
my ability to get life Discussing potential impact on life
insurance insurance? What does it cost? Pricing and reimbursement
issues Instruction on self-assessment Instructions for performing
assessment Instruction on completing informed consent Instructions
for completing informed consent Instruction for providing a sample
Instructions for obtaining sample Instructions for labeling sample
Is this test covered by my insurance? Instructions for self-payment
or reimbursement Should I pay for this directly? Should I claim
reimbursement? Instructions for completing medical record Who to
contact for more information Additional instructional materials
Test results Background on informed consent Referalls to health
care providers Background information on patterns of inheritance
(WITH DIAGRAM) Background information on genes, DNA, chromosomes
(WITH DIAGRAM) Background information on cardiovascular system
(WITH DIAGRAM) Background on psychosocial issues in genetic testing
Background on the potential for genetic discrimination Answers to
frequently asked questions CERTIFICATION ELEMENT RECORDING ELEMENT
COLLECTION ELEMENT Checklist LABELING ELEMENT BILLING ELEMENT
Checklist Question 1 result Question 1 result Question 2 result
Question 2 result Question 3 result Question 3 result Qustion 4
result Qustion 4 result h Quesxtion 5 result Quesxtion 5 result
Question 6 result Question 6 result Question 7 result Question 7
result Question 8 result Question 8 result Medical and Family
History Worksheet Subjective assessment of healthcare concerns
Personal medical history Review of systems Family tree/geneology
Family medical history Question 9 result Question 9 result Question
10 result Question 10 result Informed content form Text Signature
pages (duplicate) Materials for labeling sample Personal
identification/deidentification Label to affix to sample Contact
information for reporting results Billing forms self pay forms
reimbursement claim forms Checklist for medical records assesssment
medical history worksheet family history worksheet informed consent
(signed) contact information for reporting results
TABLE-US-00007 TABLE IV INFORMED CONSENT FOR PHARMACOGENETIC
TESTING INSTRUCTION ELEMENT Why informed consent is an important
part of genetic testing Instructions on use of this instrument for
patient instruction Instructions on use of this instrument for
informed consent Checklist (shorksheet) INFORMATION ELEMENT
Instructions to be provided to individuals ASSESSMENT ELEMENT How
my genes may affect the safety and effectiveness Instructional
materials on genetic affects on 1 Which of the following ARE NOT
true? of the drugs I take drug action (a) Durgs may have different
effects in different people (b) My response to a drug may be
affected by my genes (c) Drugs approved by the FDA are always safe
(d) The safety of a drug I take may be affected by my genes (e) The
effectiveness of a drug I take may be affected by my genes Genes
may affect how drugs are taken up and activated Describing genetic
effects on ADME (text and 2 Which of the following ARE NOT true
about genetic tests for drug safety and effectiveness? in my body
diagram) (a) Tests can predict how quickly my body can break down
certain drugs Genes may affect how drugs are activated in my body
Describing the effect of genetic variation in (b) Tests can predict
how quickly my body can activate certain drugs the target of drug
action (c) Tests can tell me whether all the drugs I take are safe
and effective Genes may affect how a certain drug works for me
Describing the association of certain genes with (d) Tests can help
my doctor choose a drug and dose that is right for me Genes may
affect how drugs are broken down and specific drug toxicities (e)
Tests can help me and my doctor avoid drug interactions eliminated
from my body Genes may determine whether a scertain drug is par-
ticularly risky for me What is genetic variation? Why is is
relevent to drug Instructional materials on genetic variation
action? Everyone's genes contain variations Normal genetic
variation 3 Which of the following ARE true about genetic tests
Some variations may cause disease The concept of mutation and
normal polymor- (a) Genetic tests only identify mutations that
cause genetic disease phism (b) Since I have always been healthy, I
don't have any genetic variations Most variations are normal and
contribute to our indi- Patterns of inheritance (c) If I have not
been exposed to carcinogenes or radition, I probably don't have any
variations viduality (d) Everyone has thousands of genetic
variations that may affect health Genetic variations is inherited
but may not be apparent Variable expression in different
individuals and (e) If my family members do not have drug toxicity,
I don't have to worry in every person gneerations How can
information from a genetic test be used to im- Instructional
materials on the application of test prove my care results How my
doctor can use information from a genetic test How physicians can
use test results to choose 4 Which of the following ARE NOT true
about how my doctor may use the genetic test result? to choose
drugs that are most likely to be safe and appropriate therapies (a)
My doctor may use the results to choose among different drugs for
treating my disease effective for me Choosing alternative drugs
from a class of drugs (b) My doctor may alter the dose of a drug
that is customized for my needs Choosing the appropriate dose and
form of the (c) My doctor may avoid giving me certain drugs drug
(d) My doctor will be able to guarantee that the drugs which are
prescribed are safe Monitoring drug levels and effect (e) My doctor
may choose to monitor the level of a drug in my blood How I can use
the information from a genetic test to Improving compliance with
prescribed drugs 5 Which of the following ARE NOT true about how I
will be able to use the genetic test results avoid drug
sensitivities and toxicity (a) Inform my doctor that I have had the
test before receiving any prescription Care in choosing over the
counter medications (b) Be aware of potential sensitives to certain
drugs Care in the use of herbal remedies (c) Take a smaller dose of
all drugs to be sure they are safe Care in choice of diet (d) Avoid
certain over-the-counter medicines or herbal remedies (e) Watch
certain elements of my diet What does my medical history and family
history tell me Instructions on completing medical history and
about my risk? family history My history of previous drug use,
sensitivity, or toxicity Family history of drug sensitivity or
toxicity How is a genetic test performed Instructional materials on
how genetic tests are peformed What is informed consent? Describing
the purpose and regulations regarding 6 Which of the following ARE
NOT generally considered steps in performing a genetic test?
informed consent (a) Obtaining a sample from a cheek swab or blood
sample (b) Sending the sample to a laboratory (c) Extracting DNA
from a sample (d) Storing DNA from the sample (e) Inserting new
genetic materials into a sample (f) Reporting restuls of the test
to the subject (g) Reporting results of the rest to the referring
physician How do I provide a sample for testing? Describing the
testingprocess How is this sample handled? What happens to the
sample Describing sample handing procedures after the test is
completed? Who performs the test? Describing sample testing
procedures Who receives the test results? Describing policies
regarding medical record privacy and distribution Does anyone else
have to know the test results? 7 Which of the following statements
ARE NOT true? (a) genetic testing can not be performed wihtout your
consent (b) samples are used only for the purpose described in the
consent (c) samples can be sold for research without your consent
(d) samples can be saved for additional testing in the future (e) a
health professional in the laboratory will check the test results
(f) it is recommended to meet with a provider to review test
results (g) your medical records can not be sent to anyone without
consent How will I know what to do when I receive the test Describe
the follow-up process results? What is genetic counseling? Describe
genetic counseling and referral pro- cedures Why is follow-up very
important? Describe importance of follow-up and pro- ceedures
Should I have this test performed? Guiding the individual's choice
whether or not 8. Which of the following statements ARE NOT true?
to perform a test (a) Many durg sensitivities are due to genetic
variations (b) If my relatives have had drug sensitivities or
toxicity, I am more likely to have these also (c) If no one in my
family has a history of drug sensitivity or toxicity, I don't need
to worry (d) If I tend to be sensitive to drugs, it is possible
this sensitivity is due to a genetic effect (e) Genetic tests can
not guarantee that every drug I take will be safe or effective (f)
If I have genetic variations causing drug sensitivity, my relatives
may have the same variations Does my medical history or family
history indicate an Instructions on predicing risk from medical/
increased risk family history Am I taking drugs, or am I likely to
take drugs affected by genetic variation Recommendation of experts
in the field Recommendations of the NIH risk and profes- 9 Which of
the following ARE NOT true about genetic tests to identify
variations in 2D6? sional societies (a) -5-10% of all individuals
in the US have variations in 2D6 that may affect drug action (b)
Variations in 2D6 tht affect drug action are less common in African
Americans (c) Any potential variation in 2D6 can be detected by
genetic testing (d) Variations in 2D6 may make codeine an
ineffective medicine for some people (e) Variations in 2D6 may
alter my response to certain drugs for anxiety or depression (f)
Variations in 2D6 may alter my response to some over the counter
medicines Should my family members be tested also? Guding a
discussion on whether to discuss test with family members What are
the benefits of performing this genetic test? Describing the
benefits of identifying genetic risk factors What are the risks of
performing this genetic test? Describing the risks of identifying
genetic risk 10 Which of the following ARE NOT prohibited by law?
factors (a) hiring or firing based on a genetic test result (b)
denying health insurance or health care based on a genetic test (c)
performing a genetic test without an individuals consent (d) giving
test results to employer without an individuals consent (e) keeping
test results secret from employers, family, or friends Do I want to
know this information? Describing emotional and practical
implications of identifying risk factors Will I act on this
information? Will a positive test affect my ability to get a job?
Describing laws against discrimination and nationwide experience
Will a positive test affect my ability to get health Describing
laws against discrimination insurance? Will a positive test affect
my ability to get life Discussing potential impact on life
insurance insurance? What does it cost? Pricing and reimbursement
issues Instruction on self-assessment Instructions for performing
assessment Corect answers to assessment Instructions for scoring
assessment Instructions for further instruction and assessment
Instructions on completing informed consent Instructions for
completing informed consent Instructions for providing a sample
Instructions for obtaining sample Instructions for labeling sample
Is this test covered by my insurance? Instructions for self-payment
or reimbursement Should I pay for this directly? Should I claim
reimbursement? Instructions for completing medical record Who to
contact for more information Additional instructional materials
Test results Background on informed consent Referalls to health
care providers Tables of genetic effects on commonly used drugs
Long-term follow-up about new tests and new drugs Background
information on patterns of inherit- ance (WITH DIAGRAM) Background
information on genes, DNA, chromosomes (WITH DIAGRAM) Background on
psychosocial issues in genetic testing Background on the potential
for genetic discrimi- nation Answers to frequently asked questions
CERTIFICATION ELEMENT RECORDING ELEMENT COLLECTION ELEMENT
Checklist LABELING ELEMENT BILLING ELEMENT Checklist Question 1
result Question 1 result Qustion 2 result Question 2 result
Quedstion 3 result Question 3 result Question 4 result Question 4
result Question 5 result Question 5 result Medical and Family
History Worksheet Medical and Family History Worksheet Personal
medical History Personal medical history History of drug
sensitivity or toxicity History of drug sensitivity or toxicity
Review of systems Review of systems Family tree/geneology Family
tree/geneology Family medical history Family medical history
Question 6 result Quedstion 6 result Question 7 result Question 7
result Question 8 result Question 8 result Question 9 result
Question 9 result Question 10 result Question 10 result Assessment
score Assessment score Informed consent form Text Signature pages
(duplicate)
Materials for labeling sample Personal
identification/deidentification Label to affix to sample Contact
information for reporting results Billing forms self pay forms
authorization for information release reimbursement claim forms
Checklist for medical record assessment medical history worksheet
family history worksheet informed consent (signed) contact
information for reporting results consent for long-term follow-up
contact information for follow-up
* * * * *
References